Endovascular catheters and methods for carotid body ablation

ABSTRACT

Systems, devices, and methods for treating a patient having a sympathetically mediated disease associated at least in part with augmented peripheral chemoreflex or heightened sympathetic activation. The treatments include ablating one or more peripheral chemoreceptors or associated afferent nerves to reduce or remove afferent neural signals from the peripheral chemoreceptor.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/214,222, filed Jul. 19, 2016, now U.S. Pat. No. 9,757,180, which is acontinuation of U.S. patent application Ser. No. 13/869,765, filed Apr.24, 2013, now U.S. Pat. No. 9,393,070, which application claims priorityto the following U.S. Provisional Patent Applications, the disclosuresof which are incorporated by reference herein in their entireties: U.S.Provisional Application No. 61/637,582, filed Apr. 24, 2012; U.S.Provisional Application No. 61/643,243, filed May 5, 2012; U.S.Provisional Application No. 61/644,620, filed May 9, 2012; and U.S.Provisional Application No. 61/794,667, filed Mar. 15, 2013.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference to the same extent as if eachindividual publication or patent application was specifically andindividually indicated to be incorporated by reference.

BACKGROUND

An imbalance of the autonomic nervous system is associated with severaldisease states. Restoration of autonomic balance has been a target ofseveral medical treatments including modalities such as pharmacological,device-based, and electrical stimulation. For example, beta blockers area class of drugs used to reduce sympathetic activity to treat cardiacarrhythmias and hypertension; Gelfand and Levin (U.S. Pat. No.7,162,303) describe a device-based treatment used to decrease renalsympathetic activity to treat heart failure, hypertension, and renalfailure; Yun and Yuarn-Bor (U.S. Pat. Nos. 7,149,574; 7,363,076;7,738,952) describe a method of restoring autonomic balance byincreasing parasympathetic activity to treat disease associated withparasympathetic attrition; Kieval, Burns and Serdar (U.S. Pat. No.8,060,206) describe an electrical pulse generator that stimulates abaroreceptor, increasing parasympathetic activity, in response to highblood pressure; Hlavka and Elliott (US 2010/0070004) describe animplantable electrical stimulator in communication with an afferentneural pathway of a carotid body chemoreceptor to control dyspnea viaelectrical neuromodulation.

Devices are needed that are configured to be positioned in the vicinityof a carotid body and are adapted to ablate the carotid body or relatedstructure to treat one or more sympathetically mediated diseases.

SUMMARY OF THE DISCLOSURE

The disclosure includes methods, devices, and systems for endovascularinterstitial ablation of a carotid body. Endovascular interstitialablation of a carotid body generally refers to delivering a devicethrough a patient's vasculature to a vessel proximate a peripheralchemosensor (e.g., carotid body) or an associated nerve of the patient,and passing an ablation element from the device through the vessel wallinto interstitial space (e.g., intercarotid septum) to ablate theperipheral chemosensor.

A carotid body may be ablated by placing an ablation needle into a lumenof a carotid artery adjacent to the carotid body of interest, insertingthe ablation needle into the periarterial space containing the carotidbody, delivering an ablation agent into the periarterial space by meansof the needle, withdrawing the needle from the periarterial space backinto the carotid artery.

A carotid body may also be ablated by placing an ablation needle into alumen of a carotid artery adjacent to the carotid body of interest,inserting the needle into periarterial space containing the carotidbody, delivering an ablation agent into the periarterial space by theneedle, withdrawing the needle from the periarterial space back into thecarotid artery, whereby electrosurgical current is provided at a tipregion of the needle to facilitate insertion, and heat is applied to theneedle tract prior to or during withdrawal to reduce or preventbleeding.

In another exemplary procedure a location of periarterial spaceassociated with a carotid body is identified, and ablation parametersare selected, an ablation needle is placed into a lumen of a carotidartery in proximity of the carotid body of interest, the ablation needleis inserted into the periarterial space containing the carotid body, anablation agent is delivered into the periarterial space by means of theneedle, the needle is withdrawn from the periarterial space back intothe carotid artery, whereby position of the ablation needle within theperiarterial space and selection of ablation parameters provides forablation of the carotid body without substantial collateral damage toadjacent functional structures.

In a further exemplary procedure a location of periarterial spaceassociated with a carotid body is identified, as well as location ofvital structures not associated with the carotid body, and based onthese locations ablation parameters are selected, an ablation needle isplaced into a lumen of a carotid artery in proximity of the carotid bodyof interest, the needle is inserted into the periarterial spacecontaining the carotid body, an ablation agent is delivered into theperiarterial space by means of the needle, the needle is withdrawn fromthe periarterial space back into the carotid artery, whereby theposition of the ablation needle within the periarterial space and theselection of ablation parameters provides for ablation of the carotidbody or a nerve associated with carotid body located in the periarterialspace without substantial collateral damage to adjacent functionalstructures.

In a further example, ablation agents for needle delivery intoperiarterial space comprising a carotid body include chemicals selectedfor thrombogenic properties, chemicals selected for sympathetic neuraltoxicity, chemicals selected for glomus cell toxicity, tissue heatingenergies including radiofrequency energy, microwave energy, ultrasonicenergy, laser energy, or resistive element heating.

Selectable carotid body ablation parameters may include ablation needletemperature, duration of ablation agent delivery, ablation energy power,ablation needle position within periarterial space, ablation needlesize, type of ablation agent delivered, volume of ablation agentdelivered, or ablation needle insertion tract.

The location of periarterial space associated with a carotid body may bedetermined by means of a non-fluoroscopic imaging procedure prior tocarotid body ablation, where the non-fluoroscopic location informationis translated to a coordinate system based on fluoroscopicallyidentifiable anatomical and/or artificial landmarks.

The function of a carotid body may be stimulated and at least onephysiological parameter recorded prior to and during the stimulation,the carotid body is ablated, and the stimulation is repeated, whereby achange in recorded physiological parameter(s) prior to and afterablation is an indication of the effectiveness of the ablation.

A function of a carotid body may be blocked and at least onephysiological parameter(s) recorded prior to and during the blockade,the carotid body is ablated, and the blockade is repeated, whereby achange in recorded physiological parameter(s) prior to and afterablation is an indication of the effectiveness of the ablation.

In an exemplary method, a device configured to prevent embolic debrisfrom entering the brain is deployed in an internal carotid arteryassociated with a carotid body, an ablation needle is inserted intoperiarterial space containing the carotid body, an ablation agent isdelivered into periarterial space with the ablation needle, the ablationneedle is then withdrawn from the periarterial space, the embolicprevention device is withdrawn from the internal carotid artery, wherebythe device in the internal carotid artery prevents debris resulting fromuse of the ablation needle from entering the brain.

In an exemplary method the location of the periarterial space associatedwith a carotid body is identified, then an ablation needle is insertedinto a predetermined location within the periarterial space from acarotid artery, ablation parameters are selected and an ablation agentis delivered into the periarterial space with the needle in accordancewith the selected parameters, the ablation needle is withdrawn into thecarotid artery and reinserted into the periarterial space in at leastone additional predetermined location, an ablation agent is deliveredusing the same or different ablation parameters, whereby the positionsof the ablation needle within the periarterial space and the selectionof ablation parameters provides for ablation of the carotid body withoutsubstantial collateral damage to adjacent functional structures.

In an exemplary embodiment a system comprises a catheter deviceconfigured with an ablation needle positioned in a vicinity of a distalend of the catheter device, and a connection between the ablation needleto a source of an ablation agent at a proximal end of the catheterdevice, whereby the distal end of the catheter is constructed to beinserted into a peripheral artery of a patient and maneuvered into acarotid artery using standard fluoroscopic guidance techniques.

In an exemplary embodiment a system includes a carotid artery catheterconfigured with an ablation needle in a vicinity of a distal end of thecatheter configured for carotid body ablation and further configured forat least one of the following: neural stimulation, neural blockade,carotid body stimulation or carotid body blockade; and a connectionbetween the ablation needle to a source of an ablation agent,stimulation agent or blockade agent located in a vicinity of a proximalend of the catheter.

Stimulation agents may include chemicals that stimulate nerves,chemicals that stimulate carotid body function, electrical energyconfigured for nerve stimulation, or electrical energy configured forcarotid body stimulation.

Blockade agents may include chemicals that blockade nerve function,chemicals that blockade carotid body function, electrical energyconfigured for blockade of nerve function, or electrical energyconfigured for blockade of carotid body function.

In some embodiments a system comprises a carotid artery catheterconfigured with an ablation needle and at least one electrode positionedproximate a distal region of the catheter, configured for at least oneof the following: neural stimulation, neural blockade, carotid bodystimulation, and carotid body blockade; and at a proximal region of thecatheter a connection between the ablation needle to a source of anablation agent, and a connection between the ablation needle orelectrode(s) to a source of stimulation energy or blockade energy.

In some embodiments a carotid artery catheter includes an ablationneedle mounted in a vicinity of a distal end of the catheter configuredfor tissue heating, whereby, the ablation needle comprises at least oneablation electrode and at least one temperature sensor, and a connectionbetween the ablation needle electrode(s) and temperature sensor(s) to anablation energy source mounted in a vicinity of a proximal end of thecatheter, with the ablation energy source being configured to maintainthe ablation needle electrode at a temperature in a range of 40 to 100degrees centigrade during ablation using signals received from thetemperature sensor(s).

In some embodiments a system includes a carotid artery catheter with anablation element needle in a vicinity of a distal end of the catheterconfigured for tissue heating, whereby, the ablation needle comprises atleast one ablation electrode and at least one temperature sensor and atleast one irrigation channel, and a connection between the ablationneedle electrode(s) and temperature sensor(s) and irrigation channel(s)to an ablation energy source mounted in a vicinity of a proximal end ofthe catheter, with the ablation energy source being configured tomaintain the ablation needle electrode at a temperature in the range of40 to 100 degrees centigrade during ablation using signals received fromthe temperature sensor(s) and by providing irrigation to the vicinity ofthe ablation needle electrode.

In some embodiments a carotid artery catheter includes a deflectionmechanism comprising a user deflectable segment in a vicinity of adistal end of the catheter and a non-deflectable segment proximal to thedeflectable segment, where deflection of the deflectable segment isfacilitated by a pull wire within the catheter in communication betweenthe distal segment and a handle containing a deflection actuator at aproximal end of the catheter, and an ablation needle mounted in vicinityof the distal end, whereby the deflection mechanism is configured toprovide the user with a means for placing and holding the ablationneedle against the wall of a carotid artery for insertion of the needlethrough the artery wall into periarterial space.

A system may include a carotid artery sheath with a user deflectablesegment in vicinity of a distal end of the sheath and a non-deflectablesegment proximal to the deflectable segment, where deflection of thedeflectable segment is facilitated by a pull wire within the sheath incommunication between the deflectable segment and a handle containing adeflection actuator at a proximal end of the catheter, whereby thesheath is configured for positioning an ablation needle catheter forneedle insertion into the periarterial space containing a carotid body.

In some embodiments a carotid artery catheter comprises a forcepsstructure and an ablation needle mounted in vicinity of a distal end ofthe catheter, and a means for actuating the forceps structure and aconnection between the ablation needle to an ablation agent source, anda device located in vicinity of a proximal end of the catheter thatinserts the ablation needle into a periarterial space proximate acarotid bifurcation saddle containing a carotid body, whereby theforceps are configured to grasp and hold the carotid bifurcation saddleat a position suited for ablation needle insertion into the periarterialspace, and to facilitate the needle insertion.

In some embodiments a carotid artery catheter comprises a suction cupstructure and an ablation needle mounted in a vicinity of a distal endof the catheter, and a suction device which applies suction to thesuction cup structure and a connection between the ablation needle to anablation agent source, and an insertion device in a vicinity of aproximal end of the catheter for inserting the ablation needle into aperiarterial space containing a carotid body from within a carotidartery, whereby the suction cup and suction device are configured toattach and hold the ablation needle catheter to a carotid artery at aposition suited for ablation needle insertion into the periarterialspace, and to facilitate the needle insertion.

In some embodiments a carotid artery catheter includes a deployablestructure configured for user actuated radial expansion in vicinity of adistal end of the catheter, a radiopaque ablation needle mounted on oneside of the deployable structure and at least one radiopaque elementmounted on an opposite side of the deployable structure, whereby thedeployable structure provides the user with a means for positioning theablation needle for insertion into periarterial space comprising acarotid body, where a combination of the radiopaque ablation needle andthe radiopaque element provide the user with a substantially unambiguousfluoroscopic determination of location of the ablation needle within thecarotid artery.

In some embodiments a system adapted for endovascular interstitialablation of a carotid body includes comprising a carotid artery catheterwith an ablation needle mounted in a vicinity of a distal end of thecatheter, a means for positioning the ablation needle within a carotidartery at a specific location, a means to provide a user with asubstantially unambiguous fluoroscopic determination of position of theablation needle within a carotid artery, a means for inserting theablation needle into a periarterial space containing a carotid body topredetermined depth, a means for connecting the ablation needle to asource of an ablation agent mounted in vicinity of a proximal end of thecatheter, and a console comprising a source of an ablation agent, ameans for controlling delivery of the ablation agent, a user interfaceconfigured to provide the user with a selection of ablation parameters,indications of status of the console and status of ablation activity, ameans to activate and deactivate an ablation, and an umbilical toprovide a means for connecting the catheter to the console.

In some embodiments a method reduces or inhibit chemoreflex functiongenerated by a carotid body in a mammalian patient, to reduce afferentnerve sympathetic activity of carotid body nerves to treat asympathetically mediated disease, the method comprising: positioning acatheter in a vascular system of the patient such that a distal sectionof the catheter is in a lumen proximate to the carotid body of thepatient; advancing an ablation element from the lumen into anintercarotid septum the carotid body or at least a portion of a carotidbody; supplying energy to the ablation element wherein the energy issupplied by an energy supply apparatus outside of the patient; applyingthe energy from the energy supply to the ablation element to ablatetissue proximate to or included in the carotid body; and removing theablation device from the patient; wherein a carotid body chemoreflexfunction is inhibited or sympathetic afferent nerve activity of carotidbody nerves is reduced due to the ablation.

In some embodiments a method to treat a patient having a sympatheticallymediated disease by reducing or inhibiting chemoreflex functiongenerated by a carotid body includes the steps of inserting a catheterinto the patient's vasculature, positioning a portion of the catheterproximate a carotid body (e.g., in a carotid artery, pointing atrajectory of a deployable interstitial ablation needle toward a targetablation site (e.g., carotid body, intercarotid septum, carotid plexus,carotid sinus nerve), holding position of the catheter, inserting adeployable interstitial ablation needle into tissue, piercing a vesselwall with the interstitial ablation needle, applying ablative energy tothe target ablation site via the interstitial ablation needle,retracting the interstitial ablation needle from tissue, applying heatto tissue from the interstitial ablation needle while retracting it fromtissue to seal a puncture in the vessel, and removing the catheter fromthe patient's vasculature.

The disclosure also includes methods, devices, and systems forendovascular transmural ablation of a carotid body. Endovasculartransmural ablation of a carotid body generally refers to delivering adevice through a patient's vasculature to a blood vessel proximate to aperipheral chemosensor (e.g., carotid body) or an associated nerve ornerve plexus of the patient and placing an ablation element associatedwith the device against the internal wall of the vessel adjacent to theperipheral chemosensor and activating the ablation element to ablate theperipheral chemosensor.

A carotid body may be ablated by placing an ablation element within andagainst the wall of a carotid artery adjacent to the carotid body ofinterest, then activating the ablation element causing a change in thetemperature of the periarterial space containing the carotid body to anextent and duration sufficient to ablate the carotid body.

A carotid body may also be ablated by placing an ablation element withinand against the wall of an internal jugular vein adjacent to the carotidbody of interest, then activating the ablation element causing a changein the temperature of the perivenous space containing the carotid bodyto an extent and duration sufficient to ablate the carotid body.

In another exemplary procedure a location of periarterial spaceassociated with a carotid body is identified, then an ablation elementis placed against the interior wall of a carotid artery adjacent to theidentified location, then ablation parameters are selected and theablation element is activated thereby ablating the carotid body, wherebythe position of the ablation element and the selection of ablationparameters provides for ablation of the carotid body without substantialcollateral damage to adjacent functional structures.

In a further exemplary procedure a location of perivenous spaceassociated with a carotid body is identified, then an ablation elementis placed against the interior wall of an internal jugular vein adjacentto the identified location, then ablation parameters are selected andthe ablation element is activated thereby ablating the carotid body,whereby the position of the ablation element and the selection ofablation parameters provides for ablation of the carotid body withoutsubstantial collateral damage to adjacent functional structures.

In further example the location of the periarterial space associatedwith a carotid body is identified, as well as the location of vitalstructures not associated with the carotid body, then an ablationelement is placed against the interior wall of a carotid artery adjacentto the identified location, ablation parameters are selected and theablation element is then activated thereby ablating the carotid body,whereby the position of the ablation element and the selection ofablation parameters provides for ablation of the target carotid bodywithout substantial collateral damage to vital structures in thevicinity of the carotid body.

In another example the location of the perivenous space associated witha carotid body is identified, as well as the location of vitalstructures not associated with the carotid body, then an ablationelement is placed against the interior wall of an internal jugular veinadjacent to the identified location, ablation parameters are selectedand the ablation element is then activated thereby ablating the carotidbody, whereby the position of the ablation element and the selection ofablation parameters provides for ablation of the target carotid bodywithout substantial collateral damage to vital structures in thevicinity of the carotid body.

Selectable carotid body ablation parameters include ablation elementtemperature, duration of ablation element activation, ablation power,ablation element force of contact with a vessel wall, ablation elementsize, ablation modality, and ablation element position within a vessel.

The location of the perivascular space associated with a carotid bodycan be determined by means of a non-fluoroscopic imaging procedure priorto carotid body ablation, where the non-fluoroscopic locationinformation is translated to a coordinate system based onfluoroscopically identifiable anatomical and/or artificial landmarks.

A function of a carotid body can be stimulated and at least onephysiological parameter is recorded prior to and during the stimulation,then the carotid body is ablated, and the stimulation is repeated,whereby the change in recorded physiological parameter(s) prior to andafter ablation is an indication of the effectiveness of the ablation.

A function of a carotid body can be temporarily blocked and at least onephysiological parameter(s) is recorded prior to and during the blockade,then the carotid body is ablated, and the blockade is repeated, wherebythe change in recorded physiological parameter(s) prior to and afterablation is an indication of the effectiveness of the ablation.

In some embodiments a device configured to prevent embolic debris fromentering the brain is deployed in an internal carotid artery associatedwith a carotid body, then an ablation element is placed within andagainst the wall of the external carotid artery associated with thecarotid body, the ablation element is activated resulting in carotidbody ablation, the ablation element is then withdrawn from the externalcarotid artery, then the embolic prevention device is withdrawn from theinternal carotid artery, whereby the device in the internal carotidartery prevents debris resulting from the use of the ablation elementform entering the brain.

In some embodiments a method includes identifying a location of theperivascular space associated with a carotid body, then an ablationelement is placed in a predetermined location against the interior wallof vessel adjacent to the identified location, then ablation parametersare selected and the ablation element is activated and then deactivated,the ablation element is then repositioned in at least one additionalpredetermine location against the same interior wall and the ablationelement is then reactivated using the same or different ablationparameters, whereby the positions of the ablation element and theselection of ablation parameters provides for ablation of the carotidbody without substantial collateral damage to adjacent functionalstructures.

In some embodiments the location of the perivascular space associatedwith a carotid body is identified, an ablation element configured fortissue freezing is placed against the interior wall of a vessel adjacentto the identified location, ablation parameters are selected forreversible cryo-ablation and the ablation element is activated, theeffectiveness of the ablation is then determined by at least onephysiological response to the ablation, and if the determination is thatthe physiological response is favorable, then the ablation element isreactivated using the ablation parameters selected for permanent carotidbody ablation.

Some embodiments includes a system that comprises a vascular catheterconfigured with an ablation element in the vicinity of the distal end,and a connection between the ablation element and a source of ablationenergy at the proximal end, whereby the distal end of the catheter isconstructed to be inserted into a peripheral artery of a patient andthen maneuvered into an internal or external carotid artery usingstandard fluoroscopic guidance techniques.

Some embodiments includes a device that comprises a catheter configuredwith an ablation element in the vicinity of the distal end, and a meansto connect the ablation element to a source of ablation energy at theproximal end, whereby the distal end of the catheter is constructed tobe inserted into a peripheral vein of a patient and then maneuvered intoan internal jugular vein using standard fluoroscopic guidancetechniques.

Some embodiments includes a system comprising a vascular catheterconfigured with an ablation element in the vicinity of the distal endconfigured for carotid body ablation and further configured for at leastone of the following: neural stimulation, neural blockade, carotid bodystimulation and carotid body blockade; and a connection between theablation element and a source of ablation energy, stimulation energyand/or blockade energy.

Some embodiments includes a system comprising a vascular catheterconfigured with an ablation element and at least one electrodeconfigured for at least one of the following: neural stimulation, neuralblockade, carotid body stimulation and carotid body blockade; and aconnection between the ablation element to a source of ablation energy,and a connection between the ablation element and/or electrode(s) to asource of stimulation energy and/or blockade energy.

Some embodiments includes a system comprising a vascular catheter withan ablation element mounted in the vicinity of the distal end configuredfor tissue heating, whereby, the ablation element comprises at least oneelectrode and at least one temperature sensor, a connection between theablation element electrode(s) and temperature sensor(s) to an ablationenergy source, with the ablation energy source being configured tomaintain the ablation element at a temperature in the range of 40 to 100degrees centigrade during ablation using signals received from thetemperature sensor(s).

Some embodiments includes a system comprising a vascular catheter withan ablation element mounted in the vicinity of the distal end configuredfor tissue heating, whereby, the ablation element comprises at least oneelectrode and at least one temperature sensor and at least oneirrigation channel, and a connection between the ablation elementelectrode(s) and temperature sensor(s) and irrigation channel(s) to anablation energy source, with the ablation energy source being configuredto maintain the ablation element at a temperature in the range of 40 to100 degrees centigrade during ablation using signals received from thetemperature sensor(s) and by providing irrigation to the vicinity of theablation element.

Some embodiments includes a system comprising a vascular catheter withan ablation element mounted in the vicinity of the distal end configuredfor tissue freezing, whereby, the ablation element comprises at leastone cryogenic expansion chamber and at least one temperature sensor, anda connection between the ablation element expansion chamber andtemperature sensor(s) to a cryogenic agent source, with the cryogenicagent source being configured to maintain the ablation element at apredetermined temperature in the range of −20 to −160 degrees centigradeduring ablation using signals received from the temperature sensor(s).

Some embodiments includes a system comprising a vascular catheter withan ablation element mounted in the vicinity of the distal end configuredto freeze tissue, and to heat tissue, whereby, the ablation elementcomprises at least one cryogenic expansion chamber constructed of anelectrically conductive material and configured as an electrode, and atleast one temperature sensor, and a connection between the ablationelement expansion chamber/electrode and temperature sensor(s) to anablation source consisting of cryogenic agent source and an electricalheating energy source.

Some embodiments include a carotid artery catheter with a userdeflectable segment in the vicinity of the distal end and anon-deflectable segment proximal to the deflectable segment, where thedeflection of the distal segment is facilitated by a pull wire withinthe catheter in communication between the distal segment and a handlecontaining a deflection actuator at the proximal end, and an ablationelement mounted in the vicinity of the distal end, whereby thedeflection mechanism is configured to provide the user with a means forplacing the ablation element against the wall of a carotid artery.

Some embodiments include a jugular vein catheter a user deflectablesegment in the vicinity of the distal end and a non-deflectable segmentproximal to the deflectable segment, where the deflection of the distalsegment is facilitated by a pull wire within the catheter incommunication between the distal segment and a handle containing adeflection actuator at the proximal end, and an ablation element mountedin the vicinity of the distal end, whereby the deflection mechanism isconfigured to provide the user with a means for placing the ablationelement against the wall of a jugular vein.

Some embodiments include a carotid artery sheath with a user deflectablesegment in the vicinity of the distal end and a non-deflectable segmentproximal to the deflectable segment, where the deflection of the distalsegment is facilitated by a pull wire within the sheath in communicationbetween the distal segment and a handle containing a deflection actuatorat the proximal end, and an ablation element mounted in the vicinity ofthe distal end, whereby the deflection mechanism is configured toprovide the user with a means for placing the ablation element againstthe wall of a carotid artery.

Some embodiments include a jugular vein sheath with a user deflectablesegment in the vicinity of the distal end and a non-deflectable segmentproximal to the deflectable segment, where the deflection of the distalsegment is facilitated by a pull wire within the sheath in communicationbetween the distal segment and a handle containing a deflection actuatorat the proximal end, and an ablation element mounted in the vicinity ofthe distal end, whereby the deflection mechanism is configured toprovide the user with a means for placing the ablation element againstthe wall of a jugular vein.

Some embodiments include a procedural kit for ablation of a carotid bodycomprising a carotid artery sheath with a user deflectable distalsection, an ablation element mounted in the vicinity of the distal end,and a carotid artery catheter constructed for use through the sheathconfigured to prevent debris caused by use of the sheath from enteringthe brain through the internal carotid artery associated with thecarotid body.

Some embodiments include a procedural kit for ablation of a carotid bodycomprising a vascular sheath with a user deflectable distal section, anablation element mounted in the vicinity of the distal end, and anultrasonic imaging catheter constructed for use through the sheath andconfigured to image the carotid body and surrounding anatomy as a meansfor guiding the user in the placement of the ablation element as well asimage a change in the carotid body and surrounding anatomy as a resultof the ablation in real time as a means for providing the user with anindication of the progress and/or effectiveness of the ablation.

Some embodiments include an vascular ultrasonic imaging cathetercomprises an imaging element in the vicinity of the distal endconfigured for circumferential ultrasonic imaging at an angle between−15 degrees and −50 degrees from normal, and further configured forimaging: a carotid body from within a vessel proximate to the carotidbody, vital and non-vital anatomical structures in the vicinity of thecarotid body, and a change in a carotid body in real time due to anablation of the carotid body.

Another aspect of this disclosure is a vascular catheter with astructure configured for user actuated radial expansion in the vicinityof the distal end, a radiopaque ablation element mounted on one side ofthe structure and at least one radiopaque element mounted on theopposite side of the structure, whereby the structure provides the userwith a means for pressing the ablation element against the wall of avessel, and the combination of the radiopaque ablation element and theradiopaque element provide the user with a substantially unambiguousfluoroscopic determination of the location of the ablation elementwithin the vessel.

Some embodiments include a carotid artery catheter with a forcepsstructure comprising at least two arms configured for user actuation inthe vicinity of the distal end, a radiopaque ablation element mounted onat least one arm of the structure and at least one radiopaque element onthe opposite arm of the structure, whereby the structure provides theuser with a means for pressing the ablation element against the wall ofa carotid artery, and the combination of the radiopaque ablation elementand the radiopaque element provide the user with a substantiallyunambiguous fluoroscopic determination of the location of the ablationelement within a carotid artery.

Some embodiments include a system for endovascular transmural ablationof a carotid body comprising a carotid artery catheter with an ablationelement mounted in the vicinity of the distal end, a means for pressingthe ablation element against the wall of a carotid artery at a specificlocation, a means for providing the user with a substantiallyunambiguous fluoroscopic determination of the position of the ablationelement in a carotid artery, a means for connecting the ablation elementto a source of ablation energy mounted in the vicinity of the proximalend, and a console comprising a source of ablation energy, a means forcontrolling the ablation energy, a user interface configured to providethe user with a selection of ablation parameters, indications of thestatus of the console and the status of the ablation activity, a meansto activate and deactivate an ablation, and an umbilical to provide ameans for connecting the catheter to the console.

Some embodiments include a method to reduce or inhibit chemoreflexfunction generated by a carotid body in a mammalian patient, to reduceafferent nerve sympathetic activity of carotid body nerves to treat asympathetically mediated disease, the method comprising: positioning acatheter in a vascular system of the patient such that a distal sectionof the catheter is in a lumen proximate to the carotid body of thepatient; pressing an ablation element against the wall of the lumenadjacent to the carotid body, supplying energy to the ablation elementwherein the energy is supplied by an energy supply apparatus outside ofthe patient; applying the energy from the energy supply to the ablationelement to ablate tissue proximate to or included in the carotid body;and removing the ablation device from the patient; wherein a carotidbody chemoreflex function is inhibited or sympathetic afferent nerveactivity of carotid body nerves is reduced due to the ablation.

Some embodiments include a method to treat a patient having asympathetically mediated disease by reducing or inhibiting chemoreflexfunction generated by a carotid body including steps of inserting acatheter into the patient's vasculature, positioning a portion of thecatheter proximate a carotid body (e.g., in a carotid artery),positioning an ablation element toward a target ablation site (e.g.,carotid body, intercarotid septum, carotid plexus, carotid sinus nerve),holding position of the catheter, applying ablative energy to the targetablation site via the ablation element, and removing the catheter fromthe patient's vasculature.

The methods and systems disclosed herein may be applied to satisfyclinical needs related to treating cardiac, metabolic, and pulmonarydiseases associated, at least in part, with enhanced chemoreflex (e.g.,high chemosensor sensitivity or high chemosensor activity) and relatedsympathetic activation. The treatments disclosed herein may be used torestore autonomic balance by reducing sympathetic activity, as opposedto increasing parasympathetic activity. It is understood thatparasympathetic activity can increase as a result of the reduction ofsympathetic activity (e.g., sympathetic withdrawal) and normalization ofautonomic balance. Furthermore, the treatments may be used to reducesympathetic activity by modulating a peripheral chemoreflex.Furthermore, the treatments may be used to reduce afferent neuralstimulus, conducted via afferent carotid body nerves, from a carotidbody to the central nervous system. Enhanced peripheral and centralchemoreflex is implicated in several pathologies including hypertension,cardiac tachyarrhythmias, sleep apnea, dyspnea, chronic obstructivepulmonary disease (COPD), diabetes and insulin resistance, and CHF.Mechanisms by which these diseases progress may be different, but theycan commonly include contribution from increased afferent neural signalsfrom a carotid body. Central sympathetic nervous system activation iscommon to all these progressive and debilitating diseases. Peripheralchemoreflex may be modulated, for example, by modulating carotid bodyactivity. The carotid body is the sensing element of the afferent limbof the peripheral chemoreflex. Carotid body activity may be modulated,for example, by ablating a carotid body or afferent nerves emerging fromthe carotid body. Such nerves can be found in a carotid body itself, ina carotid plexus, in an intercarotid septum, in periarterial space of acarotid bifurcation and internal and external carotid arteries, andinternal jugular vein. Therefore, a therapeutic method has beenconceived that comprises a goal of restoring or partially restoringautonomic balance by reducing or removing carotid body input into thecentral nervous system.

One aspect of the disclosure is an ablation catheter adapted to beadvanced endovascularly to a bifurcation of an internal carotid arteryand an external carotid artery comprising: a forceps structurecomprising at least two arms configured for user actuation, the firstarm configured to engage with a wall of the internal carotid arterydelimiting a carotid septum and the second arm configured to besimultaneously engaged with a wall of the external carotid arterydelimiting the carotid septum; and an ablation element mounted on atleast one arm of the structure, the ablation element configured toablate at least a portion of the carotid septum.

In some embodiments the forceps structure includes means for pressingthe ablation element against a wall of a carotid artery at a specificlocation adjacent the carotid septum. The first and second arms can beconfigured so that a force of contact distends the ablation elementabout 1 mm to 3 mm into a wall of a carotid artery. In some embodimentsthe forceps structure includes means for pressing the ablation elementagainst a wall of a carotid artery. In some embodiments the ablationelement is positioned on the arm such that it engages a wall of theinternal or external carotid artery delimiting a carotid septum. In someembodiments the ablation element comprises a surface adapted to contacta vessel wall adjacent the carotid septum.

In some embodiments the ablation element is an electrode disposed on thefirst or the second arm. In some embodiments the first and second armsare adapted to compress the carotid septum. In some embodiments thecatheter comprises an arm actuator adapted to move the first and secondarms towards each other. In some embodiments the first and second armsare further adapted to move away from each other toward a presetposition.

In some embodiments the ablation element comprises a first electrodedisposed on the first arm and a second electrode disposed on the secondarm. In some embodiments the first and second arms are adapted to movefrom an undeployed configuration to a deployed configuration in whichthe first and second arms are further apart than in the undeployedconfiguration. In some embodiments the catheter includes a sheathadapted to contain the first and second arms during endovascularadvancement. A functional sheath diameter can be between 3 French and 12French. In some embodiments the first and second arms are adapted tomove toward the deployed configuration as they emerge from the sheath.In some embodiments the sheath is adapted to be advanced toward thefirst and second arms to move the first and second arms toward eachother.

In some embodiments the ablation element is configured to heat thetarget tissue to a temperature above 37° C., and in some embodiments theablation element is configured to heat the target tissue to atemperature above 45° C.

In some embodiments the catheter further comprises one or moretemperature sensors positioned at the first and/or second arms.

In some embodiments the catheter is configured to be positioned againstthe carotid bifurcation saddle to position the ablation element at apredetermined distance distal of the carotid bifurcation saddle. In someembodiments the catheter is configured to place the ablation elementagainst the wall of a carotid artery at a position no more than 15 mmdistal to the carotid bifurcation saddle.

In some embodiments a system includes an ablation catheter, an ablationsource operably connected to the ablation element of the ablationcatheter, and a user control comprising an ablation actuator operativeto deliver an ablation agent from the ablation source to the ablationelement to ablate the target tissue. The ablation source can comprise anRF generator. The ablation element can comprise a first electrodedisposed on the first arm and a second electrode disposed on the secondarm, and wherein the first and second electrodes are connected toopposite poles of the RF generator or to the same poles of the RFgenerator. The user control can be configured to specify or calculatetreatment parameters to control a desired ablation.

One aspect of the disclosure is an ablation catheter adapted to beadvanced endovascularly to a bifurcation of an internal carotid arteryand an external carotid artery adjacent a carotid septum, the cathetersupporting an ablation element for ablating target tissue and first andsecond arms, the first arm being adapted to engage with a wall of theexternal carotid artery adjacent the carotid septum, and the second armbeing adapted to simultaneously engage with a wall of the internalcarotid artery adjacent the carotid septum, to support the ablationelement in a position to ablate target tissue within the carotid septum,wherein the catheter is connectable to an ablation source.

The first and second arms can be further adapted to press the ablationelement into contact with a carotid artery wall. The first and secondarms can be configured so that a force of contact distends the ablationelement about 1 mm to 3 mm into a wall of a carotid artery. The cathetercan includes means for pressing the ablation element into contact with awall of a carotid artery. The ablation element can comprise a surfaceadapted to contact a vessel wall adjacent the carotid septum.

The ablation element can be an electrode disposed on the first or thesecond arm. The first and second arms can be further adapted to positionthe ablation element into contact with the vessel wall at a bifurcationbetween the external carotid artery and the internal carotid artery.

The ablation element can comprise a sharp distal point adapted topenetrate through the vessel wall into the carotid septum.

The first and second arms can be further adapted to compress the carotidseptum. The catheter can further comprise an arm actuator adapted tomove the first and second arms towards each other. The first and secondarms can be further adapted to move away from each other toward a presetposition.

The ablation element can comprise a first electrode disposed on thefirst arm and a second electrode disposed on the second arm.

The first and second arms can be further adapted to move from anundeployed configuration to a deployed configuration in which the firstand second arms are further apart than in the undeployed configuration.The catheter can also include a sheath adapted to contain the first andsecond arms during endovascular advancement. A functional sheathdiameter can be between 3 French and 12 French. The first and secondarms can be adapted to move toward the deployed configuration as theyemerge from the sheath. The sheath can be adapted to be advanced towardthe first and second arms to move the first and second arms toward eachother.

In some embodiments the ablation element is configured to heat thetarget tissue to a temperature above 37° C., and in some embodiments theablation element is configured to heat the target tissue to atemperature above 45° C.

The catheter can include one or more temperature sensors positioned atthe first and/or second arms.

The catheter can be configured to be positioned against the carotidbifurcation saddle to position the ablation element at a predetermineddistance distal of the carotid bifurcation saddle. The catheter can beconfigured to place the ablation element against the wall of a carotidartery at a position no more than 15 mm distal to the carotidbifurcation saddle.

One aspect of the disclosure is an ablation catheter adapted to beadvanced endovascularly to a bifurcation of an internal carotid arteryand an external carotid artery comprising: an ablation device comprisingat least two arms configured for user actuation, the first armconfigured to engage with a wall of the internal carotid arterydelimiting a carotid septum and the second arm configured to besimultaneously engaged with a wall of the external carotid arterydelimiting the carotid septum; and an ablation element mounted on atleast one arm, the ablation element configured to ablate at least aportion of the carotid septum. Exemplary embodiments of this aspect aredescribed above.

One aspect of the disclosure is an ablation method for ablating targettissue within a carotid septum of a patient, the method comprising:advancing an ablation device into an artery of a patient, the ablationdevice comprising first and second arms and an ablation element; passingthe first arm into an external carotid artery of the patient and intoengagement with a wall of the external carotid artery adjacent a carotidseptum; passing the second arm into an internal carotid artery of thepatient and into engagement with a wall of the internal carotid arteryadjacent the carotid septum; and actuating the ablation element toablate target tissue within the carotid septum.

The method can further comprise contacting the ablation element with avessel wall adjacent the carotid septum. Contacting the ablation elementwith a vessel wall adjacent the carotid septum can comprise contactingthe ablation element with a vessel wall no more than 15 mm distal to acarotid bifurcation saddle.

The method can further comprise inserting the ablation element into thecarotid septum. The contacting step can comprise contacting the vesselwall at a bifurcation between the external carotid artery and theinternal carotid artery.

The first and second arms can support the ablation element in contactwith the vessel wall.

The method can include grasping the carotid septum with the first andsecond arms. The method can include compressing the carotid septum withthe first and second arms.

The actuating step can be performed during the compressing step.

The method can also include moving the first and second arms away fromeach other. The advancing step can comprise advancing the ablationdevice with the first and second arms in an undeployed configuration,the moving step comprising moving the first and second arms away fromeach other from the undeployed configuration to a deployedconfiguration. The advancing step can comprise advancing the first andsecond arms within a sheath. The moving step can comprise permitting thefirst and second arms to return toward a preset position.

The method can also include moving the first and second arms toward eachother. The moving step can include operating an arm actuator.

The actuating step can comprise actuating the ablation element to ablatethe target tissue while the first and second arms are engaged with theartery walls.

In some embodiments at least part of the ablation element is disposed onthe first arm or the second arm. The ablation element can comprise firstand second electrodes, the first electrode being disposed on the firstarm and the second electrode being disposed on the second arm, theactuating step comprising using the first and second electrodes toablate the target tissue with RF energy. The first and second electrodescan be connected to the same pole of an RF generator, or they can beconnected to opposite poles of an RF generator. The ablation element cancomprise a pair of bipolar electrodes.

The actuating step can comprise heating the target tissue to atemperature above 37° C. The actuating step can comprise heating thetarget tissue to a temperature above 45° C. The actuating step cancomprise delivering ablation energy from the ablation element to thetarget tissue for 30-120 seconds.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic view showing endovascular access of a catheter toa left common carotid artery of a patient.

FIG. 2 is a schematic view of a steerable sheath.

FIG. 3 is a schematic view of a steerable sheath in a deflected state.

FIG. 4 is a cutaway illustration of a lateral view a patient's rightcarotid artery system with a schematic view of a steerable sheathpositioning a distal region proximate a target penetration site.

FIGS. 5A and 5B are schematic views showing endovascular access of acatheter to a left common carotid artery of a patient.

FIG. 6 is an exploded view of a radiofrequency electrode needle.

FIG. 7 is a schematic view of an endovascular catheter having aradiofrequency electrode needle.

FIG. 8 is a cutaway illustration of a lateral view a patient's rightcarotid artery system with a schematic view of an endovascular catheterhaving a radiofrequency electrode needle inserted into a target site.

FIG. 9 is a schematic view of an interstitial RF perforation, ablationand sealing device.

FIG. 10 is an exploded view of an interstitial RF perforation, ablationand sealing device.

FIGS. 11A and 11B are schematic views of an interstitial RF perforation,ablation and sealing device.

FIG. 12 is a cutaway illustration of a lateral view of a patient's rightcarotid artery system with a schematic view of an endovascular catheterhaving a curved radiofrequency electrode needle inserted into a targetsite.

FIG. 13 is a cutaway illustration of a lateral view a patient's rightcarotid artery system with a schematic view of an endovascular catheterhaving a radiofrequency electrode needle with a helical curvatureinserted into a target site.

FIG. 14 is a schematic view of an interstitial RF ablation catheter withside exiting guide wires.

FIG. 15 is a cutaway illustration of a lateral view a patient's rightcarotid artery system with a schematic view of an ablation catheter,with side exiting guide wires, positioning an ablation element forinterstitial ablation of a carotid body.

FIG. 16 is a schematic view of an endovascular ablation catheter havingdeployable arms.

FIG. 17 is a cutaway illustration of a lateral view of a patient's rightcarotid artery system with a schematic view of an endovascular ablationcatheter having deployable arms positioned in the patient's internal andexternal carotid arteries for interstitial ablation of a carotid body.

FIG. 18 is a schematic view of an endovascular ablation catheter havinga suction element and an interstitial radiofrequency electrode.

FIG. 19 is a cutaway illustration of a lateral view a patient's rightcarotid artery system with a schematic view of an endovascular ablationcatheter having a suction element and an interstitial radiofrequencyelectrode positioned in a carotid septum for interstitial ablation of acarotid body.

FIG. 20 is a schematic view of an interstitial laser ablation needle.

FIG. 21 is a schematic view of an interstitial microwave ablationneedle.

FIG. 22 is a schematic view of an interstitial ultrasound ablationneedle.

FIG. 23 is a schematic view of an interstitial chemical ablation needle.

FIG. 24A is a schematic view of a steerable sheath.

FIG. 24B is a schematic view of a steerable sheath in a deflected state.

FIG. 25 is a schematic view of a steerable sheath with an ablationelement.

FIG. 26 is a schematic view of a steerable sheath with an ablationelement in a deflected state.

FIG. 27 is a cutaway illustration of a lateral view a patient's rightcarotid artery system with a schematic view of a steerable sheathpositioning an ablation element proximate a target ablation site.

FIG. 28 is a schematic view of a distal protection balloon.

FIG. 29 is a cutaway illustration of a lateral view a patient's rightcarotid artery system with a schematic view of a steerable sheathpositioning an ablation element on an inner wall of an internal carotidartery to transmurally ablate a carotid body, and a distal protectionballoon delivered through the sheath.

FIG. 30 is a schematic view of an ablation catheter with side exitingguide wires.

FIG. 31 is a schematic view of an ablation catheter with a side exitingguide wire

FIG. 32 is a cutaway illustration of a lateral view a patient's rightcarotid artery system with a schematic view of an ablation catheter,with side exiting guide wires, positioning an ablation element on aninner wall of a carotid bifurcation to transmurally ablate a carotidbody.

FIG. 33 is a cutaway illustration of a lateral view a patient's rightcarotid artery system with a schematic view of an ablation catheter,with side exiting guide wires, positioning an ablation element on aninner wall of an external carotid artery to transmurally ablate acarotid body.

FIGS. 34A, 34B, 34C and 34D are schematic views of an endovascularablation catheter having deployable arms with ablation elements.

FIG. 35 is a cutaway illustration of a lateral view a patient's rightcarotid artery system with a schematic view of an endovascular ablationcatheter having deployable arms with ablation elements positioned in thepatient's internal and external carotid arteries for transmural ablationof a carotid body.

FIG. 36 is a cutaway illustration of a lateral view a patient's rightcarotid artery system with a schematic view of an endovascular ablationcatheter having deployable arms with ablation elements positioned in thepatient's external carotid artery for transmural ablation of a carotidbody.

FIG. 37 is a schematic view of an endovascular ablation catheter havinga suction element with a radiofrequency electrode on a contact surfaceof the suction element.

FIG. 38 is a cutaway illustration of a lateral view a patient's rightcarotid artery system with a schematic view of an endovascular ablationcatheter having a suction element with a radiofrequency electrode on acontact surface of the suction element positioned on a carotidbifurcation for transmural ablation of a carotid body.

FIG. 39 is a schematic view of an endovascular ablation catheter havinga suction element with a radiofrequency electrode on a contact surfaceof the suction element.

FIG. 40 is a flow chart of an algorithm for operating an endovascularablation catheter having a suction element with a radiofrequencyelectrode.

FIG. 41 is a schematic view of an endovascular ablation catheter havinga side suction element with a radiofrequency electrode.

FIG. 42 is a cutaway illustration of a lateral view a patient's rightcarotid artery system with a schematic view of an endovascular ablationcatheter having a side suction element with a radiofrequency electrodepositioned in an external carotid artery for transmural ablation of acarotid body.

FIGS. 43A, 43C, 43D, and 43E illustrate an endovascular catheter havinga deployable balloon and an ablation element, in an undeployed state.

FIG. 43B is a schematic view of an endovascular catheter having adeployable balloon and an ablation element, in a deployed state.

FIG. 44 is a schematic view of an endovascular catheter having adeployable balloon and bipolar radiofrequency electrodes, in a deployedstate.

FIG. 45 is a cutaway illustration of a lateral view a patient's rightcarotid artery system with a schematic view of an endovascular ablationcatheter having a deployable balloon with an ablation element positionedin the patient's external carotid artery for transmural ablation of acarotid body.

FIGS. 46A, 46B, 46C, and 46D show an endovascular catheter having adeployable balloon and an ablation element, in a deployed state.

FIG. 47 is a schematic view of an endovascular catheter having adeployable balloon and an ablation element, in a deployed state.

FIG. 48 is a schematic view of an endovascular catheter having adeployable balloon and an ablation element, in a deployed state.

FIG. 49 is a cutaway illustration of a lateral view a patient's rightcarotid artery system with a schematic view of an endovascular ablationcatheter having a cooled deployable balloon with an ablation elementpositioned in the patient's external carotid artery for transmuralablation of a carotid body.

FIGS. 50Ai, 50Aii, 50Aiii, 50Aiv, 50B, and 50C illustrate an occludingballoon catheter mounted with electrodes adapted to operate in bipolarmode.

FIGS. 51Ai and 51Aii are schematic views of an endovascular catheterhaving a deployable wire basket and an ablation element, in anundeployed state.

FIG. 51B is a schematic view of an endovascular catheter having adeployable wire basket and an ablation element, in a deployed state.

FIG. 52 is a cutaway illustration of a lateral view a patient's rightcarotid artery system with a schematic view of an endovascular catheterhaving a deployable wire basket in a deployed state, and having anablation element positioned in the patient's external carotid artery fortransmural ablation of a carotid body.

FIGS. 53A and 53B are schematic views of a back-looking intravascularultrasound guidance catheter having an ablation element.

FIG. 54 is a cutaway illustration of a lateral view a patient's rightcarotid artery system with a schematic view of a back-lookingintravascular ultrasound guidance catheter and having an ablationelement positioned in the patient's external carotid artery fortransmural ablation of a carotid body.

FIG. 55A is a schematic view of an endovascular ablation catheterconfigured for transmural cooled radiofrequency ablation of a carotidbody.

FIG. 55B is an exploded view of an endovascular ablation catheterconfigured for transmural cooled radiofrequency ablation of a carotidbody.

FIG. 56 is a cutaway illustration of a lateral view a patient's rightcarotid artery system with a schematic view of a steerable endovascularablation catheter configured for transmural cooled radiofrequencyablation of a carotid body.

FIGS. 57A and 57B are schematic views of an endovascular ablationcatheter configured for transmural cooled radiofrequency ablation of acarotid body.

FIG. 58A is a schematic view of an endovascular ablation catheter havinga point-ablate cryogenic ablation element, contained in a steerablesheath, showing an ice ball formed around the cryogenic ablationelement.

FIG. 58B is a schematic view of a steerable endovascular ablationcatheter having a point-ablate cryogenic ablation element showing an iceball formed around the cryogenic ablation element.

FIG. 59 is a schematic view of an endovascular ablation catheter havinga point-ablate cryogenic ablation element.

FIG. 60 is a cutaway illustration of a lateral view a patient's rightcarotid artery system with a schematic view of an endovascular ablationcatheter having a point-ablate cryogenic ablation element, contained ina sheath, showing an ice ball formed around the cryogenic ablationelement.

FIG. 61A is a cutaway illustration of a lateral view of a patient'sright internal jugular vein with a schematic view of an endovascularablation catheter positioned for transmural ablation of a carotid bodyfrom within the jugular vein.

FIGS. 61B and 61C are cross sectional views of a patient's internal andexternal carotid arteries, carotid body and internal jugular vein withan endovascular ablation catheter positioned for transmural ablation ofa carotid body from within the jugular vein.

FIG. 62 is a schematic illustration of a carotid body ablation catheterhaving a deployable helix.

FIG. 63 is a schematic illustration of a carotid body ablation catheterhaving a deployable loop.

DETAILED DESCRIPTION

The present disclosure is directed generally to systems and methods fortreating patients having a sympathetically mediated disease associatedat least in part with augmented peripheral chemoreflex or heightenedsympathetic activation. The treatments include ablating one or moreperipheral chemoreceptors or associated afferent nerves to reduce orremove afferent neural signals from the peripheral chemoreceptor. Whenthe disclosure indicates that the peripheral chemoreceptor is ablated,it may be referring to the chemoreceptor and/or the associated afferentnerves.

The carotid body is a small cluster of chemoreceptors (also known asglomus cells) and supporting cells located near, and in most casesdirectly at, the medial side of the bifurcation (fork) of the carotidartery, which runs along both sides of the throat.

These organs act as sensors detecting different chemical stimuli fromarterial blood and triggering an action potential in the afferent fibersthat communicate this information to the Central Nervous System (“CNS”).In response, the CNS activates reflexes that control heart rate (HR),renal function and peripheral blood circulation to maintain the desiredhomeostasis of blood gases, O₂ and CO₂, and blood pH. This closed loopcontrol function that involves blood gas chemoreceptors is known as thecarotid body chemoreflex (“CBC”). The CBC is integrated in the CNS withthe carotid sinus baroreflex (CSB) that maintains arterial bloodpressure. In a healthy organism these two reflexes maintain bloodpressure and blood gases within a narrow physiologic range. Chemosensorsand barosensors in the aortic arch contribute redundancy and fine-tuningfunction to the closed loop chemoreflex and baroreflex. In addition tosensing blood gasses, the carotid body is now understood to be sensitiveto blood flow and velocity, blood pH and glucose concentration. Thus itis understood that in conditions such as hypertension, congestive heartfailure (“CHF”), insulin resistance, diabetes and other metabolicderangements, afferent signaling of carotid body nerves may be elevated.Carotid body hyperactivity may be present even in the absence ofdetectable hypersensitivity to hypoxia and hypercapnia that aretraditionally used to index carotid body function.

Some exemplary methods of treatment include ablating one or both carotidbodies or associated afferent nerves via endovascular access to removeor reduce afferent neural signals from a carotid body and reduce carotidbody contribution to central sympathetic tone. The disclosure hereinfocuses on ablating carotid bodies and associated afferent nerves, butit is not intended to be so limiting.

The expected reduction of chemoreflex activity and sensitivity tohypoxia and other stimuli such as blood flow, blood CO₂, glucoseconcentration or blood pH can directly reduce afferent signals fromchemoreceptors and produce at least one beneficial effect such as thereduction of central sympathetic activation, reduction of the sensationof breathlessness (dyspnea), vasodilation, increase of exercisecapacity, reduction of blood pressure, reduction of sodium and waterretention, redistribution of blood volume to skeletal muscle, reductionof insulin resistance, reduction of hyperventilation, reduction oftachypnea, reduction of hypocapnia, increase of baroreflex andbarosensitivity of baroreceptors, increase of vagal tone, or improvesymptoms of a sympathetically mediated disease and may ultimately slowdown the disease progression and extend life. It is understood that asympathetically mediated disease that may be treated with carotid bodyablation may comprise elevated sympathetic tone, an elevatedsympathetic/parasympathetic activity ratio, autonomic imbalanceprimarily attributable to central sympathetic tone being abnormally orundesirably high, or heightened sympathetic tone at least partiallyattributable to afferent excitation traceable to hypersensitivity orhyperactivity of a peripheral chemoreceptor (e.g., carotid body). Insome important clinical cases where baseline hypocapnia or tachypnea ispresent, reduction of hyperventilation and breathing rate may beexpected. It is understood that hyperventilation in the context hereinmeans respiration in excess of metabolic needs on the individual thatgenerally leads to slight but significant hypocapnea (blood CO₂ partialpressure below normal of approximately 40 mmHg, for example in the rangeof 33 to 38 mmHg).

Sympathetically mediated diseases that can be treated using the devices,systems, and methods herein include, without limitation, cardiac, renal,metabolic, and pulmonary diseases such as, for example, hypertension,congestive heart failure (“CHF”), sleep apnea, sleep disorderedbreathing, diabetes or insulin resistance).

To inhibit or suppress a peripheral chemoreflex, anatomical targets forablation (also referred to herein as targeted tissue, target ablationsites, target sites, or derivatives thereof) may include at least aportion of at least one carotid body, an aortic body, nerves associatedwith a peripheral chemoreceptor (e.g., carotid body nerves, carotidsinus nerve, carotid plexus), small blood vessels feeding a peripheralchemoreceptor, carotid body parenchyma, chemosensitive cells (e.g.,glomus cells), tissue in a location where a carotid body is suspected toreside (e.g., based on pre-operative imaging or anatomical likelihood),an intercarotid septum, a substantial part of an intercarotid septum, orany combination thereof.

As used herein, “interstitial space” includes, without limitation, anintercarotid septum, periarterial space, perivenous space, andextravascular space.

An intercarotid septum (also referred to herein as a carotid septum) isa wedge or triangular segment of tissue with the followingboundaries: 1) the saddle of the carotid bifurcation defines the caudalaspect (an apex) of the carotid septum; the facing walls of the internaland external carotid arteries define two of the sides of the carotidseptum; a cranial boundary of the carotid septum extends between thesearteries and is 10 mm-15 mm from the saddle of the carotid bifurcation;and the medial and lateral walls of the carotid septum are generallydefined by two-dimensional planes tangent to the internal and externalcarotid arteries. One of the planes is tangent to the lateral wall ofthe internal and external carotid arteries and the other plane istangent to the medial walls of these arteries. The carotid septum isbetween the medial and lateral walls. As shown in FIG. 4, anintercarotid septum 114 may contain a carotid body and may be absent ofvital structures such as a vagus nerve or hypoglossal nerve. Anintercarotid septum may additionally include some baroreceptors andbaroreceptor nerves.

Carotid body nerves are anatomically defined herein as carotid plexusnerves and carotid sinus nerves. Carotid body nerves are functionallydefined herein as nerves that conduct information from a carotid body toa central nervous system.

An ablation may be focused exclusively on targeted tissue, or be focusedon the targeted tissue while safely ablating tissue proximate to thetargeted tissue (e.g., to ensure the targeted tissue is ablated or as anapproach to gain access to the targeted tissue). An ablation may be asbig as the peripheral chemoreceptor (e.g., carotid body or aortic body)itself, somewhat smaller, or bigger and can include tissue surroundingthe chemoreceptor such as, for example, blood vessels, adventitia,fascia, small blood vessels perfusing the chemoreceptor, or nervesconnected to and innervating the glomus cells. An intercarotid plexus orcarotid sinus nerve may be a target of ablation with an understandingthat some baroreceptor nerves will be ablated together with carotid bodynerves. Baroreceptors are distributed in the human arteries and havehigh degree of redundancy.

An embodiment of a therapy may substantially reduce chemoreflex withoutexcessively reducing the baroreflex of the patient. The proposedablation procedure may be targeted to substantially spare the carotidsinus, baroreceptors distributed in the walls of carotid arteries(specifically internal carotid artery), and at least some of the carotidsinus nerves that conduct signals from said baroreceptors. For example,the baroreflex may be substantially spared by targeting a limited volumeof ablated tissue possibly enclosing the carotid body, tissuescontaining a substantial number of carotid body nerves, tissues locatedin periadventitial space of a medial segment of a carotid bifurcation,tissue located at the attachment of a carotid body to an artery, orextending to tissues located on the medial side of a carotid arterybifurcation saddle and avoiding damage to the lateral side. The carotidsinus baroreflex is accomplished by negative feedback systemsincorporating pressure sensors (e.g., baroreceptors) that sense thearterial pressure. Baroreceptors also exist in other places, such as theaorta and coronary arteries. Important arterial baroreceptors arelocated in the carotid sinus, a slight dilatation of the internalcarotid artery at its origin from the common carotid. The carotid sinusbaroreceptors are close to but anatomically separate from the carotidbody. Baroreceptors respond to stretching of the arterial wall andcommunicate blood pressure information to CNS. Baroreceptors aredistributed in the arterial walls of the carotid sinus while thechemoreceptors (glomus cells) are clustered inside the carotid body.This makes the selective reduction of chemoreflex described in thisapplication possible while substantially sparing the baroreflex. In theablation therapies herein, however, sparing the baroreflex may not be anecessary feature of the therapy because the carotid baroreflex is quiteforgiving and can return quickly if injured.

In some embodiments tissue may be ablated to inhibit or suppress achemoreflex of only one of a patient's two carotid bodies. Otherembodiments involve ablating tissue to inhibit or suppress a chemoreflexof both of a patient's carotid bodies. For example a therapeutic methodmay include ablation of one carotid body, measurement of resultingchemosensitivity, sympathetic activity, respiration or other parameterrelated to carotid body hyperactivity and ablation of the second carotidbody if needed to further reduce chemosensitivity following unilateralablation.

Said targeted ablation is enabled by visualization of the area orcarotid body itself, for example by CT, CT angiography, MRI, ultrasoundsonography, fluoroscopy, blood flow visualization, or injection ofcontrast, and positioning of an instrument in the carotid body or inclose proximity while avoiding excessive damage (e.g., perforation,stenosis, thrombosis) to carotid arteries, baroreceptors or carotidsinus nerves. Thus imaging a carotid body before ablation may beinstrumental in (a) selecting candidates if a carotid body is present,large enough and identified and (b) guiding therapy by providing alandmark map for an operator to guide an ablation instrument to carotidbody nerves, the area of a blood vessel proximate to a carotid body, orto an area where carotid body nerves may be anticipated. It may alsohelp exclude patients in whom the carotid body is located in a positionclose to a vagus nerve, hypoglossal nerve, jugular vein or some otherstructure that can be endangered by ablation. In one embodiment onlypatients with carotid body substantially located within the intercarotidseptum are selected for ablation therapy.

Once a carotid body is ablated, removed or denervated, the carotid bodychemoreflex does not substantially return in humans (in humans aorticchemoreceptors are considered undeveloped). To the contrary, once acarotid sinus baroreflex is removed it is generally compensated, afterweeks or months, by the aortic baroreceptor baroreflex. Thus, if boththe carotid chemoreflex and baroreflex are removed or substantiallyreduced, for example by interruption of the carotid sinus nerve orintercarotid plexus nerves, baroreflex may eventually be restored whilethe chemoreflex may not. The consequences of temporary removal orreduction of the baroreflex can be relatively severe and requirehospitalization and management with drugs, but they generally are notlife threatening, terminal or permanent. Thus, it is understood thatwhile selective removal of carotid body chemoreflex with baroreflexpreservation may be desired, it may not be absolutely necessary in somecases.

As used herein, “ablate,” “ablation”,” or “ablating” (generally referredto as “ablation”) refers to an intervention that alters a tissue tosuppress or inhibit its biological function or ability to respond tostimulation permanently or for an extended period of time, such asgreater than 3 weeks, greater than 6 months, greater than a year, forseveral years, or for the remainder of the patient's life. In someembodiments ablation refers to an intervention that is intended topermanently suppress or inhibit natural chemoreceptor or afferent nervefunctioning. Ablation is used herein in contrast to neuromodulation,which reversibly deactivates and reactivates chemoreceptor functioning.Ablation may involve, but is not limited to, thermal necrosis (e.g.,using energy such as thermal energy, radiofrequency electrical current,direct current, microwave, ultrasound, high intensity focusedultrasound, and laser), cryogenic ablation, electroporation, selectivedenervation, embolization (e.g., occlusion of blood vessels feeding thegland), artificial sclerosing of blood vessels, mechanical impingementor crushing, surgical removal, chemical ablation, or application ofradiation causing controlled necrosis (e.g., brachytherapy). Selectivedenervation may involve, for example, interruption of afferent nervesfrom a carotid body while preserving nerves from a carotid sinus, whichconduct baroreceptor signals. Another example of selective denervationmay involve interruption of a carotid sinus nerve, or intercarotidplexus which is in communication with both a carotid body andbaroreceptors wherein chemoreflex from the carotid body is reducedpermanently or for an extended period of time and baroreflex issubstantially restored.

Carotid Body Ablation (“CBA”) herein refers to ablation of a targettissue wherein the desired effect is to reduce or remove the afferentneural signaling from a chemosensor (e.g., a carotid body) or reducing achemoreflex. Chemoreflex or afferent nerve activity cannot be directlymeasured in a practical way, thus indexes of chemoreflex such aschemosensitivity can sometimes be uses instead. Chemoreflex reduction isgenerally indicated by a reduction of an increase of ventilation andventilation effort per unit of blood gas change or by a reduction ofcentral sympathetic nerve activity that can be measured indirectly.Sympathetic nerve activity can be assessed by measuring activity ofperipheral nerves leading to muscles (MSNA), heart rate (HR), heart ratevariability (HRV), production of hormones such as renin, epinephrine andangiotensin, and peripheral vascular resistance. All these parametersare measurable and can lead directly to the health improvements. In thecase of CHF patients, blood pH, blood PCO₂, degree of hyperventilationand metabolic exercise test parameters such as peak VO₂, and VE/VCO₂slope are equally important. It is believed that patients withheightened chemoreflex have low VO₂ and high VE/VCO₂ slope (index ofrespiratory efficiency) as a result of tachypnea and low blood CO₂.These parameters are also firmly related exercise limitations thatfurther speed up patient's status deterioration towards morbidity anddeath. It is understood that all these indexes are indirect andimperfect and intended to direct therapy to patients that are mostlikely to benefit or to acquire an indication of technical success ofablation rather than to provide an exact measurement of effect orguarantee a success.

CBA may include methods and systems for the thermal ablation of tissuevia thermal heating or cooling mechanisms. Thermal ablation may beachieved due to a direct effect on tissues and structures that areinduced by the thermal stress. Additionally or alternatively, thethermal disruption may at least in part be due to alteration of vascularor peri-vascular structures (e.g., arteries, arterioles, capillaries orveins), which perfuse the carotid body and neural fibers surrounding thecarotid body (e.g., nerves that transmit afferent information fromcarotid body chemoreceptors to the brain). Additionally or alternativelythermal disruption may be due to a healing process, fibrosis, orscarring of tissue following thermal injury, particularly whenprevention of regrowth and regeneration of active tissue is desired. Asused herein, thermal mechanisms for ablation may include both thermalnecrosis or thermal injury or damage (e.g., via sustained heating,convective heating or resistive heating or combination). Thermal heatingmechanisms may include raising the temperature of target neural fibersabove a desired threshold, for example, above a body temperature ofabout 37° C. e.g., to achieve thermal injury or damage, or above atemperature of about 45° C. (e.g., above about 60° C.) to achievethermal necrosis. Thermal-cooling mechanisms for ablation may includereducing the temperature of target neural fibers below a desiredthreshold (e.g., to achieve freezing thermal injury). It is generallyaccepted that temperatures below −40° C. applied over a minute or tworesults in irreversible necrosis of tissue and scar formation. It isrecognized that tissue ablation by cold involves mechanisms of necrosisand apoptosis. At a low cooling rate freeze, tissue is destroyed bycellular dehydration and at high cooling rate freeze by intracellularice formation and lethal rupture of plasma membrane.

In addition to raising or lowering temperature during thermal ablation,a length of exposure to thermal stimuli may be specified to affect anextent or degree of efficacy of the thermal ablation. F or example, thelength of exposure to thermal stimuli may be for example, longer than orequal to about 30 seconds, or even longer than or equal to about 2minutes. Furthermore, the length of exposure can be less than or equalto about 10 minutes, though this should not be construed as the upperlimit of the exposure period. A temperature threshold, or thermaldosage, may be determined as a function of the duration of exposure tothermal stimuli. Additionally or alternatively, the length of exposuremay be determined as a function of the desired temperature threshold.These and other parameters may be specified or calculated to achieve andcontrol desired thermal ablation.

In some embodiments, thermally-induced ablation of carotid body orcarotid body nerves may be achieved via direct application of thermalcooling or heating energy to the target tissue. For example, a chilledor heated fluid can be applied at least proximate to the target, orheated or cooled elements (e.g., thermoelectric element, resistiveheating element, cryogenic tip or balloon) can be placed in the vicinityof a chemosensor (e.g., carotid body). In other embodiments,thermally-induced ablation may be achieved via indirect generation orapplication of thermal energy to the target neural fibers, such asthrough application of an electric field (e.g., radiofrequency,alternating current, and direct current), high-intensity focusedultrasound (HIFU), laser irradiation, or microwave radiation, to thetarget neural fibers. For example, thermally induced ablation may beachieved via delivery of a pulsed or continuous thermal electric fieldto the target tissue such as RF and pulsed RF, the electric field beingof sufficient magnitude or duration to thermally induce ablation of thetarget tissue (e.g., to heat or thermally ablate or cause necrosis ofthe targeted tissue). Additional and alternative methods and apparatusesmay be utilized to achieve thermally induced ablation, as describedhereinafter.

An ablated tissue lesion at or near the carotid body may be created bythe application of thermal energy from an energy delivery elementproximate to the distal end of the carotid body ablation device. Theablated tissue lesion may disable the carotid body or may suppress theactivity of the carotid body or interrupt conduction of afferent nervesignals from a carotid body to sympathetic nervous system. The disablingor suppression of the carotid body reduces the responsiveness of theglomus cells to changes of blood gas composition and effectively reducesthe chemoreflex gain of the patient.

Endovascular Access:

The disclosure herein includes positioning an ablation catheter inposition within a patient's vasculature. An endovascular catheter forcarotid body ablation may be delivered into a patient's vasculature viapercutaneous introduction into a blood vessel, for example a femoral,radial, brachial artery or vein, or even via a cervical approach into acarotid artery. FIG. 1 illustrates an exemplary placement of a carotidaccess sheath 1 into a patient 2 via femoral artery percutaneous access.Sheath 1 is depicted in position for insertion of an endovascularablation catheter 3 into the vicinity of the patient's left carotidartery bifurcation 4 through central lumen 41 of carotid access sheath1. The distal end 5 of sheath 1 is shown residing in the patient's leftcommon carotid artery 6. The proximal end 7 of sheath 1 is shownresiding outside of the patient 2, with the sheath's entry point intothe patient 8 being in the vicinity of the groin 9. From the sheath'sentry point 8, the sheath enters a peripheral artery 10 (in thisembodiment a femoral artery), and traverses the abdominal aorta 11, theaortic arch 12, and into the left common carotid artery 6. The carotidaccess sheath 1 may be commercially available, or may be configuredspecifically for endovascular transmural ablation of a carotid body.Techniques for placing a carotid access sheath 1 into the position asdepicted are known. An endovascular procedure may also involve the useof a guide wire, delivery sheath, guide catheter, introducer catheter,or introducer. Furthermore, these devices may be steerable and torquable(i.e., able to conduct rotation from proximal to distal end).

Steerable sheath 150, as shown in FIG. 2 may be used to facilitate anendovascular carotid body ablation procedure. The steerable sheath 150may comprise an elongate tube 151 with a lumen 152 and a distal region153 that is controllably deflectable or deformable, as shown in FIG. 3.Deflection of a distal region (e.g., bending on a plane, deforming intoa helical configuration, selective bending toward multiple directions,or other configurations deviating from a substantially linearconfiguration) may be controlled by a user-actuated mechanism 154 at aproximal region of the steerable sheath (e.g., a lever on a handle). Asteerable sheath may facilitate navigation through tortuous vessels orbranching vessels by allowing a user to direct the distal region towarda desired vessel branch or along a vessel's tortuous path. Once thesheath is navigated to a target region a steerable sheath may be used tointroduce instruments to the vicinity of the target region (e.g., thecarotid bifurcation) to facilitate carotid body ablation, as shown inFIG. 4. Controlled deflection of the distal region may allow a user toposition said instruments at a precise target location (e.g., innersurface of a vessel wall at a carotid bifurcation, internal carotidartery, or external carotid artery). Multiple instruments may bedelivered through a steerable sheath simultaneously. For example, adistal protection catheter may first be positioned in an internalcarotid artery via delivery through a steerable sheath, and the sheathmay be retracted to a carotid bifurcation to deliver an ablationcatheter while containing a shaft of the distal protection catheter.Multiple instruments may be delivered consecutively while the steerablesheath maintains position of the distal tip.

A steerable sheath may comprise a temperature sensor (e.g.,thermocouple, thermistor, microwave or fluoroptic sensor) on an outersurface intended to be in contact with tissue of a distal region thatcan measure and control ablation temperature created by an ablationcatheter delivered through a steerable catheter. In another embodiment asteerable catheter may comprise an electrode configured to measureimpedance, which may be used to monitor ablation formation or detecttissue contact, tissue composition, presence of plaque, or position withrelatively least amount of plaque to assist in locating a suitableposition to create an ablation. Impedance is measures by passing lownon-excitatory level of alternating current through tissue and measuringcurrent and voltage. In another embodiment a steerable sheath mayprovide electrical nerve stimulation or blockade via an electrodepositioned at a distal region of the steerable sheath. Evidence ofproximity to certain nerve structures (e.g., chemoreceptors,baroreceptors, vagus nerve, hypoglossal nerve) may be provided ifstimulation current is delivered and a concomitant physiologicalresponse is elicited. A steerable sheath 150 may have an outer diameterof about 8 F to 10 F and a length of about 120 cm to 140 cm and may bemade from commonly used catheter materials such as polyurethane orPebax. The sheath may be made of layers of different materials withdesired properties (strength, lubriciousness) for jacket and liner(e.g., PTFE, FEP, PE, PEBA, Polyurethane, Nylon, customized engineeringpolymers.)

The sheath may optionally have braided reinforcement (e.g., StainlessSteel, Polyester, Nylon, Nitinol) to improve torque transmission whilemaintaining flexibility. The sheath may comprise a lumen (e.g., about 6F to 9 F diameter) to accommodate an ablation catheter and a lumencontaining a control wire used to apply a force to deflect the distalregion. A distal deflectable region of the steerable sheath may be about3 cm to 6 cm long. The distal deflectable region may comprise adeflectable structure, such as a laser cut stainless steel or Nitinoltube that is biased to bend in a desired direction when a compressiveforce is applied by the control wire. A distal tip 154 of a steerablesheath may be configured to provide atraumatic contact with vasculatureas it is passed through. For example, the distal tip may have a roundedsurface. The distal tip may further comprise an anchor for a controlwire, a stimulation electrode, or a sensor (e.g., temperature sensor,impedance sensor). A distal tip may have about the same diameter of theshaft (e.g., 8 F-10 F) and a length suitable to carry its components.For example, a distal tip may be between or including about 1 mm to 10mm long. The distal tip may be constructed from stainless steel. Thedistal tip may have an atraumatic rim or extension made of softermaterial. For embodiments having sensors a distal tip may furthercomprise a dielectric coating such as ceramic partially covering thestainless steel such that the sensor is exposed to a desired side of thesteerable sheath, for example on the side that the sheath deflectstowards, or at the distal face of the sheath. A dielectric coating mayfurther provide abrasion resistance so it slides easily throughvasculature and reduces a risk of dislodging atheromatous plaque. Acontrol wire may be anchored (e.g., welded, soldered, bonded) distal toa deflectable structure, for example it may be anchored to a distal tip154 or a distal portion of the deflectable structure 153 itself or aseparate anchor. A control wire may be made from stainless steel orother high strength wire and it may continue through a shaft 151 to aproximal region 155 of a steerable sheath where it may be connected toan actuator 154 (e.g., lever) on a handle. When a user actuates theactuator the control wire is pulled creating a compressive force to thedeflectable structure, which deflects to a compressibly biaseddirection. Optionally, a control wire that is electrically conductivemay also be used to conduct electrical current for impedancemeasurement, or sensor input. A proximal region 155 of a steerablesheath may comprise an electrical connector 156 to connect conductors ina steerable sheath to a connector cable or to an electrical source(e.g., RF generator). A proximal region of a steerable sheath may alsohave a proximal exit port 157 of a lumen 152 which may terminate with afitting such as a Touhy Borst fitting or luer fitting.

One aspect of the disclosure is a method of ablating target tissuewithin a carotid septum of a patient. In some embodiments of this aspectablating the target tissue includes performing an endovascularinterstitial carotid body ablation. Interstitial carotid body ablationincludes advancing an ablation element through a wall of a carotidartery and proximate target tissue in the carotid septum, and deliveringan ablation agent from the ablation element to the target tissue. Anexemplary interstitial ablation method includes inserting a catheter inthe patient's vascular system, positioning a distal region of thecatheter in a vessel proximate a carotid body (e.g., in a common carotidartery, internal carotid artery, external carotid artery, or at acarotid bifurcation), advancing an ablation element from the distalregion of the catheter through a wall of the carotid vessel, positioningthe ablation element proximate to a target site (e.g., a carotid body,an afferent nerve associated with a carotid body, or a peripheralchemosensor), and delivering an ablation agent from the ablation elementto ablate the target site. In interstitial carotid body ablation theablation element resides within the intercarotid septum at the time ofablation.

FIGS. 5A and 5B illustrate an exemplary method of endovascularinterstitial carotid body ablation. Exemplary endovascular catheter 403is used to deliver ablation element 440 across a vessel wall 112 toaffect target tissue in interstitial space (e.g., intercarotid septum,periarterial space, extravascular space) as shown in FIGS. 5A and 5B.The ablation element can be, for example without limitation, aradiofrequency electrode, a laser fiber, a microwave antenna, anultrasound transducer, a cryoablation element, an electroporationelectrode, or a fluid delivery needle. The ablation element may be madefrom radiopaque material or comprise a radiopaque marker and whendeployed through a vessel wall it may be visualized using fluoroscopy toconfirm position. Alternatively, a contrast solution may be injectedthrough a lumen in the ablation element to verify position in a targettissue. The ablation element may have a sharp tip capable of piercingthe elastic and strong tissue of an arterial wall or even a calcifiedarterial wall.

Interstitial RF Ablation Electrode:

In some embodiments an endovascular catheter adapted for interstitialcarotid body ablation (“CBA”) comprises an ablation element in the formof a radiofrequency (“RF”) ablation electrode. The RF ablation electrodemay be in the form of a needle with a sharp tip that pierces throughtissue. In some embodiments the electrode is delivered through a vesselwall through a separate sharp delivery needle. The ablation electrodecan also be configured for RF perforation of tissue as well as RFablation.

RF is a rapidly alternating current that ablates tissue by generatingheat in the tissue through ionic agitation, which is typicallyproportional to current density. Other factors that influencetemperature generated in tissue include heat sinks (e.g., thermalconvection due to blood flow) and tissue impedance. The volume of heatedtissue is dependent on factors such as electrode size, electrode shape,RF power, duration of RF delivery, and waveform characteristics such aspulsing. In an embodiment shown in FIGS. 5A and 5B, carotid bodyablation catheter 403 is connected by wires 109 to RF energy generator210. Generator 210 may include computer controller 110 that controls theapplication of energy to electrode 440. Reference electrode 212 isplaced on the surface of the body of patient 2. Reference electrode 212establishes a current return path to RF generator 210 for currentflowing from electrode 440, through the body of the patient and toreference electrode 212. The arrangement in which current flows throughreference electrode 212 and active electrode 440 is generally referredto as a monopolar arrangement. Reference electrode 212 has a relativelylarge surface area to minimize current density and avoid skin burns.

An energy field generator 210 may be located external to the patient.Various types of energy generators or supplies, such as electricalfrequency generators, ultrasonic generators, microwave generators, laserconsoles, and heating or cryogenic fluid supplies, may be used toprovide energy to the energy delivery element at the distal tip of thecatheter. An electrode or other energy applicator at the distal tip ofthe catheter should conform to the type of energy generator coupled tothe catheter. The generator may include computer controls toautomatically or manually adjust frequency and strength of the energyapplied to the catheter, timing and period during which energy isapplied, and safety limits to the application of energy. It should beunderstood that embodiments of energy delivery electrodes describedhereinafter may be electrically connected to the generator even thoughthe generator is not explicitly shown or described with each embodiment.

FIG. 6 illustrates RF electrode needle 441, which may be made from anelectrically conductive material (e.g., stainless steel, gold,platinum-iridium, Nitinol) and may be constructed from a hypotube with asharpened needle point 444 (see FIG. 7). The sharp point 444 of needle441 may be of a shape that creates a puncture in tissue by piercing andspreading rather than coring or cutting of tissue (e.g., cone-shape,trocar, pencil point), which may facilitate closure of the punctureafter needle retraction. The RF needle caliber may be between andincluding about 18 gauge to 28 gauge (e.g., having an outer diameterbetween and including about 1.270 mm and 0.362 mm). In one embodiment, aRF electrode is an exposed portion on a distal end of hypotube 445 thatextends about a length of a catheter and the unexposed region of thehypotube is electrically insulated with a dielectric material 446 (e.g.,polymer, PET, PEEK, Teflon). The RF electrode needle 441 may have anexposed length of between or including about 2 mm to 10 mm (e.g., about5 mm). A temperature sensor (e.g., thermocouple, thermistor, fluoropticthermometry sensor) may be located in, near, or at the surface of the RFelectrode 441. FIG. 6 is an exploded view of a RF electrode needleshowing thermocouple 214 connected to two conductors 215 and 216. Theconductors extend through the catheter body (e.g., through a lumen inhypotube 445) from the distal to proximal end and are connected to wires109 (see FIG. 5A) allowing the thermocouple to communicate with RFgenerator 210. Conductors 215 and 216 may be, for example a copper andconstantan conductor, respectively, such that joining conductors 215 and216 via solder, laser welding or the like creates a thermocouplejunction. Copper conductor 215 may be used to carry both a thermocouplesignal and deliver RF energy to the electrode 441. Alternatively, aseparate conductor (not shown) may deliver RF energy to the electrode.The temperature sensor can be thermally insulated (e.g., surrounded orimbedded in plastic) from the electrode in order to better reflecttemperature of tissue where it is in contact with tissue.

Alternatively, two electrodes may be arranged at or near the distal tipof a carotid body ablation catheter such that current flows from anactive electrode to a return electrode to create an energy field, (e.g.,an electric field) in the region adjacent the electrodes and thatablates tissue. Such an arrangement is generally referred to as abipolar configuration. Active and return electrodes may be located onthe interstitial ablation element so they are both inserted into atarget site. For example, the electrodes may be about the same size andshape and be distanced between about 0.5 mm and 4 mm apart from oneanother. Alternatively, the electrodes may be different sizes so currentdensity is greater around the smaller electrode creating a greaterthermal effect. In a bipolar arrangement a reference electrode (e.g.,the reference electrode 212 shown in FIG. 5A) is not required. Thebipolar configuration has certain advantages in shaping and directingand containing the lesion and RF energy is concentrated in a regionaround or between the two electrodes. In the bipolar configuration thereference electrode can be incorporated into the design of the needle441, catheter, sheath, or guide wire.

In another embodiment a return path for RF energy may be provided by areturn electrode that is positioned within a vessel. For example, thereturn electrode may be on a distal region of an endovascular cathetersuch as on a deployable structure in contact with an inner surface of avessel lumen, or the return electrode may be on a distal region of adelivery sheath. The return electrode may be similar in size to theactive interstitial electrode so that a bipolar RF ablation is created.Alternatively, the return electrode may be substantially larger than theactive interstitial electrode so current density is dispersed and amonopolar RF ablation is created only at the active electrode. Formationof an ablation may be controlled and shaped by position of a referenceelectrode even if high current density is present only at one electrode(e.g., interstitial electrode).

A RF ablation electrode may additionally be configured to provide cooledRF energy delivery. For example, a catheter may contain a lumen in fluidcommunication with an RF electrode to irrigate a cooling fluid (e.g.,room temperature or chilled saline) to the RF electrode. The coolingfluid may exit the RF electrode through irrigation ports. Alternatively,cooling fluid may be circulated through a cavity or lumen in a cooled RFelectrode and then circulate back through a lumen in the catheter shaftto be deposited elsewhere in the patient's vasculature or outside thebody. A cooled RF system may additionally comprise a cooling fluidsource and pump. The benefit of cooling a RF electrode may be reductionof the risk of heating blood, which may create a clot or emboli.Furthermore, cooled RF may produce ablations deeper in the tissue or mayheat the contact layers of the tissue less.

FIG. 7 illustrates an exemplary endovascular catheter for interstitialCBA, with the needle 445 shown in a deployed configuration. The catheterincludes sheath 448. While the endovascular catheter is advanced intoplacement at a region of needle deployment (e.g., near a carotidbifurcation) ablation element needle 445 is positioned inside sheath448, which protects the needle, as well as vascular structures and auser. Once the sheath 448 is in the target position, a user deploys theablation element needle from sheath 448 and into the artery wall using aneedle deployment mechanism. Sheath 448 may have a lumen 449 forcontaining the needle that is about 0.004″ to 0.010″ larger than theouter diameter of insulation 446. Sheath 448 may have a wall thicknessof about 0.004″ to 0.030″. Sheath 448 may be constructed from a polymerwith a lubricious liner (e.g., PTFE) on the inner lumen surface andouter surface to facilitate delivery through a vessel or a deliverysheath, and to facilitate movement of the ablation element within thelumen 449. Sheath 448 may further comprise a stainless steel wire coilor braid in its wall for additional strength. FIG. 8 illustrates thecatheter shown in FIG. 7 in an exemplary method of CBA. As shown in FIG.8, the catheter may be configured such that the interstitial RF ablationelectrode 445, when deployed, has an extension length 451 beyond adistal tip 450 of the sheath a distance sufficient to reach a targetsite. For example, a catheter used to deliver an interstitial ablationelement through a carotid bifurcation to a carotid body, as labeled, mayhave an extension length 451 between and including about 2 mm to 15 mm(e.g., about 10 mm).

A proximal region 453 (see FIG. 7) of the endovascular catheter forinterstitial ablation may comprise a handle 454. Optionally, handle 454may have a needle deployment mechanism that is actuated by trigger 456and can be spring loaded. Once the distal tip 450 of the sheath ispositioned and stabilized in a desired location (e.g., at a carotidbifurcation) and confirmed visually with fluoroscopy a user may actuatethe trigger 456 releasing the spring-loaded deployment mechanism whichthrusts the ablation element needle 445 from the sheath and throughtissue to a target site. The trigger may further comprise a safety means(e.g., a cover or safety latch) so the trigger is not accidentallyactuated. Alternatively a needle may be deployed by an operator bymanually pushing a proximal end of a needle hypotube, pulling a controlwire, or applying hydraulic pressure. Optionally, a handle may furthercomprise a deflection actuator 457 connected to a pull wire thatdeflects a deflectable region at a distal end of a catheter. Deflectionmay facilitate positioning of the distal tip 450 at a desired location.Optionally, a handle 454 may comprise a fluid injection port 452 incommunication with the lumen 449. The fluid injection port may be usedfor injecting contrast from the distal opening of the lumen 449 into avessel so the catheter's position on the vessel can be seen onfluoroscopy. The handle 454 may further comprise an electrical connector458 to connect the RF ablation electrode 445 and temperature sensor 214to an RF generator 210 (see FIG. 5A). An electrical connector 458 mayalso be used to connect a chemosensor electrical stimulation/blockageelectrode to a signal generator.

Interstitial RF Perforation, Ablation and Sealing Electrode:

FIGS. 9, 10, and 11 illustrate an exemplary embodiment of aninterstitial RF ablation electrode that is configured for radiofrequencyperforation to perforate a vessel wall and advance to a target ablationsite, radiofrequency ablation to ablate a target site (e.g., carotidbody), radiofrequency collagen shrinking or coagulation as the electrodeis removed from the tissue to seal the perforation. RF perforationenergy, RF ablation energy, and RF coagulation energy are similar inthat they comprise electrical current in the radiofrequency range (e.g.,about 300 to 500 kHz) that is delivered from an electrode through tissueto a return electrode. However, RF perforation energy differs from RFablation energy in that it uses a high voltage (e.g., 150-180V) appliedto a higher impedance (e.g., 2000 to 6000 Ohms) for very short durations(e.g., 1 to 3 s) raising cellular temperature above 100 degrees C. andcausing intracellular expansion and rupture. RF ablation energy isapplied to a lower tissue impedance (e.g., 150 to 300 Ohms) with a lowerpower (e.g., 4 to 10 W) and a voltage of about 35 to 50V over a longerduration (e.g., 60 to 120 s) raising tissue temperature (e.g., betweenabout 50 and 90 degrees C.) to cause cellular death (e.g., proteindenaturation or desiccation) but not rupture. RF ablation is generallyused to affect a relatively larger volume of tissue on the order ofseveral mm radius from the electrode. RF coagulation is aimed at raisingtissue temperature to approximately 60 degrees C. to denature protein,particularly collagen fibers but not necessarily killing cells, in orderto seal tissue.

Radiofrequency perforation may comprise passing a tip of an electrodethrough a vessel wall by delivering a radiofrequency current that lysesvessel wall cells. The perforation may lyse cells only in very closeproximity (e.g., a couple cells deep) of the perforation electroderendering a controlled perforation that may cause little to no damage tosurrounding tissue. Very little mechanical force may be required and theperforation electrode may be blunt. RF perforation may facilitate thedelivery of an ablation electrode through a carotid artery wall byeliminating a need to apply mechanical force that could cause tissuetenting or the electrode to miss an intended positioning. Use of a blunttipped perforation electrode increases safety compared to a sharp tip. Ablunt tip could be delivered through a sheath without a risk of cuttingthe sheath. Furthermore, it could be manipulated in a carotid arteryuntil a desired position is obtained, and then RF perforation energy maybe delivered to gently advance the electrode through the vessel wall. RFperforation energy may further be applied to advance the electrodebeyond the vessel wall through tissue until it is in close proximity orwithin a target ablation site such as a carotid body or its nerves. Forexample an RF electrode may be advanced through a carina of a carotidbifurcation and into a carotid septum. Once positioned proximate atarget site RF ablation energy may be delivered from the same electrodeor a different electrode to ablate target tissue. RF ablation energy maybe applied to ablate tissue within a radius of about 2 to 4 mm of theelectrode to effectively ablate a target carotid body or its nerveswhile avoiding thermal injury of important non-target tissues orinternal or external carotid arteries. Following ablation the electrodemay be removed from the carotid septum. Optionally, RF coagulationenergy may be applied while removing the electrode in order to seal theperforation in the vessel to reduce risk of bleeding.

FIG. 9 shows an interstitial perforation/ablation portion of anembodiment comprised for RF perforation, ablation and coagulation. Adistal tip of the interstitial perforation/ablation portion comprises aRF perforation electrode 360, which may have blunt or domed shape and adiameter of approximately 20 to 25 gauge. The RF perforation electrode360 may be separated from an RF ablation electrode 361 by an electricalinsulator 362 made, for example, from ceramic. The RF ablation electrodemay have a length of about 3 to 6 mm and a diameter of about 20 to 25gauge. The RF ablation electrode may further comprise irrigation ports363 through which saline may be irrigated to cool the electrode whichmay facilitate creation of a larger ablation. Proximal to the RFablation electrode the shaft may have an electrical insulation coating364 on its outer surface.

FIG. 10 is an exploded view of the embodiment shown in FIG. 9. Anelectrical conductor 365 may be connected to the RF perforationelectrode 360 and pass through the shaft of the catheter to a proximalend where it may be connected to a radiofrequency console via anelectrical connector. The length of the conductor 365 may beelectrically insulated so RF perforation energy is delivered only to theRF perforation electrode and not the RF ablation electrode.

FIGS. 11A and 11B are an alternative embodiment of an interstitialperforation/ablation portion of a catheter wherein an outer insulativesheath 366 may be slidably advanced over a RF ablation electrodeexposing only an RF perforation electrode 367 during the perforationstep. To further isolate the ablation electrode 369. Once theinterstitial perforation/ablation portion is positioned proximate atarget tissue the sheath 366 may be retracted to expose the RF ablationelectrode 369. As shown this embodiment also comprises an electricalinsulator 368 separating the RF perforation electrode 367 and the RFablation electrode 369. Alternatively, an RF perforation electrode maybe the same component as an RF ablation electrode and an outerinsulative sheath may be advanced to reduce the size of the electrodeduring perforation and retracted to increase the size of the electrodeduring ablation or coagulation.

Curved Interstitial RF Ablation Electrode:

In an alternative embodiment, an interstitial RF ablation electrode maybe curved in a configuration that optimizes a needle deploymenttrajectory toward a target site. A carotid body may be positioned awayfrom an axis of a catheter shaft such that advancing a straight RFablation electrode will miss the carotid body. For example, a carotidbody may be positioned toward a medial side of a carotid bifurcation andtoward an external carotid artery. The position of the carotid body maybe determined before the CBA procedure using a medical imaging modalitysuch as CTA, computer tomography or magnetic resonance imaging. Thecurved RF ablation electrode may be made from Nitinol and be constrainedto a substantially straight configuration when undeployed within aneedle sheath. As the curved RF ablation electrode is advanced from thesheath the elastic properties of the Nitinol may cause it to assume itscurved form so it is advanced away from the needle sheath axis andtoward the target site.

An example of a curved interstitial RF ablation electrode includes acurvature configured for penetration through a vessel wall at a carotidbifurcation and a trajectory toward a carotid body. A suitable RFablation electrode curvature may have a radius of curvature between andincluding about 5 mm to 20 mm (e.g., about 12 mm). Another example of asuitable curvature may place the tip of the RF electrode between about10° and 40° from a central plane between the internal and externalcarotid arteries toward a medial side. The sheath may comprise tworadiopaque markers on its distal region, which may be used to determinethe alignment of the sheath with respect to the central plane betweenthe internal and external carotid arteries prior to deploying the curvedRF electrode.

FIG. 12 illustrates a deployed configuration and exemplary position ofan exemplary curved interstitial RF ablation electrode 460 that includesa curvature configured for penetration through a vessel wall from withinan external or internal carotid artery and a trajectory toward a carotidbody. This configuration of electrode 460 acts like a hook to crosstissue of an intercarotid septum from an external to internal carotidartery. In this way fixation may be achieved and the electrode 460 maybe retained in position during ablation. The catheter includesinsulation coating 461 proximal to the exposed electrode 460, which is aconductive material.

Helical Interstitial RF Ablation Electrode:

FIG. 13 illustrates an exemplary embodiment of a CBA catheter in whichthe interstitial RF electrode has a pre-formed curvature, and in thisembodiment has a helical curvature configuration. Helical RF electrodeneedle 442 may be made from Nitinol. A sheath lumen is in communicationwith a port at a distal end of the catheter, wherein the port isdisposed on a side of the catheter such that the trajectory of thehelical RF electrode needle is in a forward direction. The side portallows the axis of the helical-shaped RF electrode to be sufficientlyaligned with the axis of sheath 443. In this embodiment, the helical RFelectrode needle 442 may be advanced into tissue like a corkscrew, whichmay provide improved stability compared to a straight electrode so thereis less risk of the electrode falling out of place. Furthermore,compared to a straight electrode, a helical RF electrode needle mayallow for a greater amount of surface area of electrode to be placedwithin a target site, which may allow for a larger ablation and improvedefficacy. This embodiment may have all of the other characteristics asthe interstitial RF ablation electrode described herein.

In some embodiments ablating target tissue within a carotid septum of apatient includes advancing an ablation device into an artery of apatient, the ablation device comprising first and second arms and anablation element, passing the first arm into an external carotid arteryof the patient and into engagement with a wall of the external carotidartery adjacent a carotid septum, passing the second arm into aninternal carotid artery of the patient and into engagement with a wallof the internal carotid artery adjacent the carotid septum, andactuating the ablation element to ablate target tissue within thecarotid septum.

An exemplary embodiment of an ablation catheter that includes first andsecond arms and an ablation element is shown in FIG. 14. The ablationcatheter comprises two side-exiting lumens 470 that provide passage forguide wires 471 (which are also described herein as “arms” and“positioning elements”) used to assist the positioning of a distal tipof catheter shaft 472 at a target penetration site (e.g., inner wall ofan internal carotid artery, external carotid artery or carotidbifurcation proximate a carotid body or carotid body nerves) and formaintaining stable position as interstitial ablation element 473 isadvanced through tissue to a target ablation site, and during energydelivery. Lumens 470 are located within a longitudinal shaft of catheter472 and exit the catheter at a proximal region and at a distal regionsuch that guide wires 471 may be slidably engaged within the lumens fromthe proximal region of the shaft to the distal region of the shaft.Distal region exit ports 477 of the lumens are positioned off-axisallowing the guide wires to exit the lumen at a pre-determined angle(e.g., between or including an angle of about 5° to 90°) to the axis ofthe catheter shaft. The distal region exit ports may be positioned onapproximately opposing sides of a catheter shaft. The guide wiresdiverge from the axis of the catheter shaft forming a “V-shape.”

FIG. 15 illustrates an exemplary method of using the ablation cathetershown in FIG. 14. The catheter shown in FIG. 14 is first positioned in acommon carotid artery labeled in FIG. 15, such as via a femoralapproach, optionally through a steerable guide sheath or with anintroducer catheter or guide wire. Guide wires 471 are then advancedfrom distal region exit ports 477, with a first guide wire beingadvanced into an internal carotid artery as shown and the second guidewire being advanced into an external carotid artery, as shown. Thecatheter shaft may be pushed forward such that the septum of the carotidbifurcation rests in the “V-shape” between the two guide wires. Thiswedging of the catheter into the carotid bifurcation septum facilitatesideal positioning of a distal tip of the catheter at a penetrationtarget site and provides stability of the catheter. As shown in FIG. 15,the two guidewires are engaging the walls of the internal and externalcarotid arteries, respectively. A needle lumen in the catheter shaft 472exits at the distal tip of the catheter at distal needle port 474.Interstitial ablation element 473 (e.g., RF electrode needle, microwaveantenna, ultrasound transducer, fluid delivery needle, cryogenicapplicator, or any other ablation element described herein) is deployedfrom distal needle port 474 and through tissue to a target ablation sitein a carotid body, as shown in FIG. 15. Ablating element 473 is thenactuated to ablate target tissue within the carotid body. Ablating thetarget tissue within the carotid body treats the sympatheticallymediated disease.

In some embodiments shaft 472 has a diameter between or including about5 F to 9 F (e.g., about 5 F to 7 F). The catheter may have a lengthbetween or including about 120 cm to 200 cm (e.g., about 120 cm to 140cm) suitable to be delivered via femoral access. The catheter shaft 472may be made from a polymer such as polyurethane or Pebax and the shaftmay comprise braided reinforcement for additional strength or torquetransmission. The shaft may also be coated with a hydrophilic or otherlubricious coating for improved slidability through a sheath orintroducer. The inner lumens of the shaft may also be coated with alubricious coating to facilitate passage of guide wires or aninterstitial ablation element. The shaft may comprise guide wire lumens,for example with a diameter between or including about 0.014″ to 0.020″.The catheter shaft 472 may further comprise a needle lumen with adiameter between or including about 0.004″ to 0.010″.

In the embodiment in FIG. 14 interstitial ablation element 473 is an RFelectrode needle, and can be the same or similar to the needle electrodedescribed in FIG. 6. The RF electrode needle may be made from anelectrically conductive material (e.g., stainless steel, gold,platinum-iridium, or Nitinol) and may be constructed from a hypotubewith a sharpened needle point 475. The RF needle may be straight orcurved. The RF needle caliber may be between and including about 18gauge to 28 gauge (e.g., having an outer diameter between and includingabout 1.270 mm and 0.362 mm). In one embodiment, a RF electrode is anexposed portion on a distal end of a hypotube that extends about alength of the catheter shaft 472 and the unexposed region of thehypotube is electrically insulated with a dielectric material 476, asshown in FIG. 14 (e.g., polymer, PET, PEEK, Teflon). The RF electrodeneedle may have an exposed length of between or including about 2 mm to10 mm, and in some embodiments is about 5 mm. A temperature sensor(e.g., thermocouple, thermistor, or fluoroptic thermometry sensor) maybe located in, near, or at the surface of the RF electrode needle. TheRF electrode needle may further comprise a temperature sensor (e.g.,thermocouple connected to two conductors). Alternatively, a temperaturesensor may be in contact with tissue and insulated from direct thermalcontact with an electrode to better reflect tissue ablation temperature.For example, a temperature sensor may protrude from an electrode. Theconductors travel through the catheter body (e.g., through a lumen in ahypotube) from the distal to proximal end and are connected to wiresallowing the temperature sensor to communicate with an RF generator 210,shown in FIG. 5A. The conductors may be, for example a copper andconstantan conductor, respectively, such that joining the conductors viasolder, laser welding or the like creates a thermocouple junction. Thecopper conductor may be used to carry both a thermocouple signal anddeliver RF energy to electrode 473. Alternatively, a separate conductor(not shown) may deliver RF energy to the electrode.

A proximal region of a RF catheter with positioning guide wires maycomprise an electrical connector containing terminals for temperaturesensor conductors or a RF delivery conductor. Furthermore, the proximalregion may comprise exit ports in communication with the guide wirelumens. The proximal region exit port may be configured with a guidewire lumen extension tube terminating with a fitting (e.g., Touhy Borstor Luer fitting).

Multiple catheters with varying distal region exit port configurationsmay be provided in a kit. For example, the varying configurations maycomprise a range of port-to-tip distances (e.g., 3 mm, 5 mm, 7 mm, 9 mm)or port exit angles (e.g., 10°, 20°, 40°, 60°). A user may select anappropriate catheter configuration depending on carotid artery geometryor position of a carotid body relative to carotid arteries.

Some embodiments of the RF ablation catheter with positioning guidewires comprises more than two lumens with distal exit ports positionedat different distances from a distal tip of the catheter. When usingsuch catheters a user may select a lumen and thus an exit port throughwhich a positioning guide wire is advanced, depending on, for example,geometry of a carotid bifurcation (e.g., angle of divergence, thicknessof septum, sharpness of bifurcation) or position of a carotid bodyrelative to a carotid bifurcation (e.g., distance from bifurcation,proximity to an internal or external carotid artery). In theseembodiments the user can thus select the most desired position for oneor more guide positioning elements depending on, for example, thepatient anatomy.

Yet another alternative embodiment of the RF catheter with positioningguide wires involves a sheath having one or more lumens for one or morepositioning guide wires. An ablation catheter may be advanced throughthe sheath and thus the distance between an RF electrode on the ablationcatheter and the guide wire exit port may be changed according toposition of a carotid body relative to a carotid bifurcation.

A deployable balloon may be used as an alternative to one or morepositioning guide wires. In a similar fashion, a positioning catheterwith a balloon may be advanced through a lumen to diverge from anablation catheter, which may facilitate stable placement of an energydelivery element (e.g., RF electrode) proximate a carotid bifurcation.The positioning catheter may be placed in an internal carotid artery andthe balloon may be deployed in the internal carotid artery approximately1 cm to 10 cm from a carotid bifurcation. The balloon may increasestability of the ablation catheter position and may further occlude theinternal carotid artery so blood flow coming from a common carotidartery passes substantially through an external carotid artery.Occlusion of the internal carotid artery during placement of theablation catheter and delivery of ablative energy may prevent debrissuch as dislodged plaque or thrombus from flowing into the internalcarotid artery and divert it to the external carotid artery. This mayprotect the patient from potential brain embolism which otherwise may becaused by debris in the blood stream. Such occlusion of an internalcarotid artery may also increase the size of a thermal ablation lesionfor the same power delivered by decreasing cooling of tissue by bloodflow.

FIG. 16 illustrates a portion of another exemplary ablation catheter.The catheter in FIG. 16, like the catheter in FIG. 14, is adapted to beused in a method of ablating target tissue within a carotid septum of apatient, wherein the method includes advancing an ablation device intoan artery of a patient, the ablation device comprising first and secondarms and an ablation element, passing the first arm into an externalcarotid artery of the patient and into engagement with a wall of theexternal carotid artery adjacent a carotid septum, passing the secondarm into an internal carotid artery of the patient and into engagementwith a wall of the internal carotid artery adjacent the carotid septum,and actuating the ablation element to ablate target tissue within thecarotid septum.

The exemplary endovascular catheter for carotid body ablation (“CBA”)shown in FIG. 16 comprises bifurcation forceps 485, which may also bereferred to herein as “arms” or “positioning elements.” The bifurcationforceps are adapted to be used for any and all of the following:grasping a carotid bifurcation septum to provide an anchor forinterstitial ablation element (e.g., a needle electrode) deployment;stimulation of a carotid body by compressing the carotid body betweeneach jaw of forceps 485; ablation of a carotid body with RF energydelivered from both jaws (i.e., an example of transmural ablation asdescribed herein) while the carotid body and intervening tissue is beingcompressed by both jaws; alignment and fixation of the catheter forinterstitial ablation needle deployment; providing electricalstimulation/blockade to a carotid body through electrodes on theforceps, which may be used for carotid body locating (e.g., maximumstimulation/blockade may be achieved when a carotid body is locatedbetween the two electrodes); and locating a carotid body by measurementof afferent signals through forceps electrodes.

FIG. 17 illustrates the catheter from FIG. 16 in an exemplary method ofuse. In some embodiments the bifurcation forceps are delivered in anundeployed configuration with the forceps and interstitial ablationelement 486 constrained within sheath 484. Once positioned in a vicinityof a carotid bifurcation, sheath 484 is retracted allowing forceps 485to elastically deploy while ablation element 486 is maintained protectedwithin the sheath. The catheter may be advanced against a carotidbifurcation with a first arm of the forceps in an internal carotidartery as shown, and the second arm of the forceps in an externalcarotid artery as shown. Sheath 484 may be advanced partially to applypressure to the forceps such that they apply a squeezing force on theintercarotid septum. As shown in FIG. 17, the arms of forceps 485 are inengagement with the walls of the internal and external carotid arteries,respectively. The ablation element 486 may be advanced from the sheathand through tissue of the carotid bifurcation into a target ablationsite in the carotid body, as shown in FIG. 17. Ablating element 486 isthen actuated to ablate target tissue within the carotid body. As setforth above, the method can also include delivering RF energy throughthe jaws to ablate the carotid body.

Interstitial Catheter with a Suction Element:

FIG. 18 illustrates another embodiment of an endovascular catheter forinterstitial CBA that comprises a suction element. Examples offunctionality of the catheter with suction element 260 may include:providing an anchoring means at a carotid bifurcation in a vicinity of acarotid body artery using suction, stimulating a carotid body byapplying suction to the ostium of the carotid body artery (e.g., suctionapplied to the carotid body artery may cause retrograde blood flowthrough the carotid body vascular bed, pulling hypoxic venous blood intothe arterioles surrounding the carotid body causing an elevation incarotid body afferent signaling and corresponding physiologicalresponse); alignment and fixation for interstitial ablation needledeployment; alignment and fixation for cannulation of a carotid bodyartery with a guide wire, micro-catheter and/or ablation probe;providing electrical stimulation/blockade to a carotid body throughelectrodes mounted on a contact surface of the suction element, whichmay be used for carotid body locating (e.g., maximumstimulation/blockade achieved when the electrodes cover or are in closeproximity to the carotid body artery); locating a carotid body bymeasurement of afferent signals through electrodes mounted on thesurface of a suction element; RF ablation of a carotid body and arteryostium using an RF electrode mounted on a contact surface of a suctionelement; discrete infusion of contrast, stimulation, blockading orchemo-ablative fluids using the suction element as positive pressureseal. It is important to maintain an ablation element in place duringablative energy delivery, which may be for example between 30 to 120seconds. Attempting to pierce an arterial wall that is resilient with aneedle may push the needle away from the wall. Therefor affixing acatheter to a wall of an artery during puncture with a needle maybenefit by maintaining position during ablation and while piercing anarterial wall.

Suction element 260 may be delivered in an undeployed configurationcontained within sheath 261. Suction element 260 may be connected to anelongated tube having lumen 263. Interstitial ablation element 262(e.g., an interstitial RF ablation needle) may be contained within lumen263. Once the distal end of the catheter is positioned near a targetpenetration site (e.g., at a carotid bifurcation) sheath 261 may beretracted, allowing suction element 260 to reconfigure to the deployedconfiguration shown in FIG. 18. Suction element 260 may then be advancedinto contact with the target penetration site with the interstitialablation element maintained within the lumen 263. Negative pressure maybe applied within the lumen 263, for example, by a syringe or suctionpump at a proximal end of the lumen 263 causing the suction element 260to adhere to the target penetration site. Interstitial ablation element262 may then be advanced from the lumen 263 through the vessel wall tothe target ablation site (e.g., carotid body) as shown in the exemplarymethod of use shown FIG. 19. Other aspects of the method of use of thecatheter shown in FIG. 18 can be found in other methods of use describedherein.

Interstitial Laser Ablation Needle:

As previously described, laser may be a suitable form of ablative energyfor interstitial CBA. FIG. 20 illustrates an exemplary CBA catheterincluding an interstitial laser ablation needle, which can beincorporated into any of the embodiments for delivering an interstitialablation element described herein, including the catheter having aneedle sheath and a spring loaded trigger actuator shown in FIGS. 7 and8, the catheter having positioning guide wires shown in FIGS. 14 and 15,the catheter having bifurcation forceps shown in FIGS. 16 and 17, andthe catheter having a suction element shown in FIGS. 18 and 19. Asshown, the catheter includes interstitial laser ablation needle 290 maybe. However, when a laser ablation needle is incorporated into otherembodiments described herein, the insertion depth is shorter than thatof a radiofrequency ablation needle. Instead of inserting a needlethrough a target site, a laser needle may be inserted such that a distaltip of the needle is pointing at the target site so that as a laserpropagation cone 291 is emitted from laser ablation needle 290, thetissue within the propagation cone is ablated. In this embodiment thesystem can include a laser console in addition to or instead of aradiofrequency generator. The laser console is adapted to deliver energyto the needle through optical fiber 292.

Potential functionality of an interstitial laser ablation needle mayinclude one or more of the following: ablating a carotid body whileminimizing collateral damage to a carotid artery by placement of a laserablation needle into extra-vascular space in close or immediateproximity of the carotid body; accessing extra-vascular space invicinity of a carotid body from within a carotid artery using a needledevice with a caliber that is known to be safe for arterial puncture;precisely controlling a laser ablation process by having an opticaltemperature sensor within a laser source console that measures blackbody radiation from the ablation zone, which is used to modulate laserenergy for optimum ablation formation; avoiding disruption of plaque,and eliminating plaque as an obstacle to carotid body ablation; usingthe electrically conductive needle as an electrode to facilitate directelectrical stimulation and/or blockade of carotid body function, orusing the electrode to sense carotid body afferent signals that may be ameasure of technical success.

Interstitial Microwave Ablation Needle:

As previously described, microwave may be a suitable form of ablativeenergy for interstitial carotid body ablation. An exemplary interstitialmicrowave ablation needle, as shown in an exploded view in FIG. 21, maybe incorporated into any of the embodiments for delivering aninterstitial ablation element described herein, including the catheterhaving a needle sheath and a spring loaded trigger actuator shown inFIGS. 7 and 8, the catheter having a curved interstitial ablation needleshown in FIGS. 12 and 13, the catheter having positioning guide wiresshown in FIGS. 14 and 15, the catheter having bifurcation forceps shownin FIGS. 16 and 17, and the catheter having a suction element shown inFIGS. 18 and 19. Similar to an interstitial radiofrequency ablationneedle (445 in FIG. 8, 442 in FIG. 13, 473 in FIG. 15, 486 in FIG. 17,and 262 in FIG. 19) an interstitial microwave ablation needle may beinserted into, near, or through an ablation target such as a carotidbody. On a proximal region of a microwave catheter the microwaveablation needle may be connected to a microwave generator with a coaxialmicrowave connector. Conductors for a temperature sensor may beconnected to the microwave generator. As shown in FIG. 21 interstitialmicrowave ablation needle 270 may be constructed from hypotube 271 madefrom a conductive material (e.g., Nitinol, stainless steel) and may havea gauge for example between and including about 18 Ga and 28 Ga (e.g.,about 25 Ga). A distal tip 274 of hypotube 271 may be sharpened tofacilitate insertion into tissue. An exposed region at a distal end ofhypotube 271 forms microwave radiation emission zone 272. Optionally,the exposed distal tip may also be used as an electrode for electorallystimulation or blockage of nerves, or for sensing nerve activity priorto or after delivery of microwave energy. When microwave energy isdelivered to the microwave radiation emission zone 272 surroundingtissue is heated. A microwave radiation emission zone length that issuitable for CBA may be between or including about 2 mm to 10 mm (e.g.,5 mm). The remaining length of the hypotube 271 may be shielded tocontain microwave radiation emission. Shielding 273 may comprise aninner dielectric layer, a middle electrically conductive layer and anouter dielectric layer. A temperature sensor 275 (e.g., thermistor,thermocouple, optic sensor) may be positioned in a lumen of the hypotube271 in the region of the microwave radiation emission zone 272. Theexploded view of FIG. 21 shows a thermocouple 275 exploded from thelumen. Thermocouple 275 may be made by joining two dissimilar metalconductors such as copper conductor 276 and constantan conductor 277.

Potential functionality of an interstitial microwave ablation needle mayinclude one or more of the following: ablating a carotid body whileminimizing collateral damage to a carotid artery by placement of amicrowave ablation electrode into extra-vascular space in close orimmediate proximity of the carotid body; accessing extra-vascular spacein vicinity of a carotid body from within a carotid artery using aneedle device with a caliber that is known to be safe for arterialpuncture; precisely controlling a microwave ablation process by having atemperature sensor within an ablation zone, which is used to modulatemicrowave energy for optimum lesion formation; avoiding disruption ofplaque, and eliminating plaque as an obstacle to carotid body ablation;and facilitating direct electrical stimulation or blockade of carotidbody function, or extra-vascular placement of an electrode for carotidbody afferent signal detection, which may be used as a measure oftechnical success.

Interstitial Ultrasound Ablation Needle:

As previously described, ultrasound may be a suitable form of ablativeenergy for interstitial carotid body ablation. An interstitialultrasound ablation needle, as shown in an exploded view in FIG. 22, maybe incorporated into any of the embodiments for delivering aninterstitial ablation element described herein, including the catheterhaving a needle sheath and a spring loaded trigger actuator shown inFIGS. 7 and 8, the catheter having a curved interstitial ablation needleshown in FIGS. 12 and 13, the catheter having positioning guide wiresshown in FIGS. 14 and 15, the catheter having bifurcation forceps shownin FIGS. 16 and 17, and the catheter having a suction element shown inFIGS. 18 and 19. Similar to an interstitial radiofrequency ablationneedle (445 in FIG. 8, 442 in FIG. 13, 473 in FIG. 15, 486 in FIG. 17,and 262 in FIG. 19) an interstitial ultrasound ablation needle may beinserted into, near, or through an ablation target such as a carotidbody.

As shown in an exploded view in FIG. 22, interstitial ultrasoundablation needle 390 may be made from a hypotube 391 (e.g., Nitinol,stainless steel) and may have a gauge for example between and includingabout 18 Ga and 28 Ga (e.g., about 25 Ga). A distal tip 392 of thehypotube 391 may be sharpened to facilitate insertion into tissue.Optionally, the hypotube may be electrically insulated with a dielectricmaterial 393 along the length of the hypotube 391 leaving an exposeddistal tip 394. The exposed distal tip may be used as an electrode forelectorally stimulation or blockage of nerves, or for sensing nerveactivity prior to or after delivery of microwave energy. Containedwithin a lumen of the hypotube 391 may be a piezoelectric crystal 395connected to an insulated center conductor 396 that is connected to anelectrical connector at a proximal region of the catheter for connectionto an ultrasound power generator. For example, the piezoelectric crystal395 may be a cylindrical shape with an outer diameter (e.g., about0.014″) that substantially matches and electrically connects with aninner diameter of the hypotube 391. The hypotube 391 may thus act as aconductor and be connected to the electrical connector at the proximalregion of the catheter for connection to the ultrasound power generator.The crystal 395 may have a lumen (e.g., about 0.006″) that fits andelectrically connects with a stripped portion of the center conductor396. The crystal 395 may have a length suitable for CBA (e.g., betweenor including about 2 mm to 10 mm, or about 5 mm). Heat is generated in atissue zone surrounding the needle by ultrasonic kinetic energyabsorption that is frequency dependent. The frequency, which may becontrolled by the generator, can be tailored for maximum thermal effect,or limited thermal effect.

Potential functionality of an interstitial ultrasound ablation needlemay include one or more of the following: ablating a carotid body whileminimizing collateral damage to a carotid artery by placement of anultrasound thermal ablation needle probe into extra-vascular space inclose or immediate proximity of the carotid body; accessingextra-vascular space in vicinity of a carotid body from within a carotidartery using a needle device with a caliber that is known to be safe forarterial puncture; creating a larger ablation zone in relation to probesize using ultrasonic thermal ablation compared to RF energy; avoidingdisruption of plaque, and eliminating plaque as an obstacle to carotidbody ablation; and the electrode may be used to facilitate directelectrical stimulation or blockade of carotid body function, or sensecarotid body afferent signals as a measure of technical success ofablation.

Interstitial Chemical Ablation Needle:

As previously described, chemical ablation may be a suitable form ofablative energy for interstitial carotid body ablation. An exemplaryinterstitial chemical ablation needle, as shown in FIG. 23, may beincorporated into any of the embodiments for delivering an interstitialablation element described herein, including the catheter having aneedle sheath and a spring loaded trigger actuator shown in FIGS. 7 and8, the catheter having a curved interstitial ablation needle shown inFIGS. 12 and 13, the catheter having positioning guide wires shown inFIGS. 14 and 15, the catheter having bifurcation forceps shown in FIGS.16 and 17, and the catheter having a suction element shown in FIGS. 18and 19. Similar to an interstitial radiofrequency ablation needle (445in FIG. 8, 442 in FIG. 13, 473 in FIG. 15, 486 in FIG. 17, and 262 inFIG. 19) an interstitial chemical ablation needle may be inserted into,near, or through an ablation target such as a carotid body. A chemicalablation needle, as shown in FIG. 23, may be made from a hypotube 381with a sharped tip that facilitates insertion through tissue. Thehypotube may be, for example about 25 Ga and made from Nitinol orstainless steel. Optionally, the needle may be insulated with a polymeror dielectric coating 382 along the length of the hypotube with anexposed region or about 5 mm at a distal end of the needle. This exposedregion may be used as an electrode.

Potential functionality of an interstitial chemical ablation needle mayinclude one or more of the following: ablating a carotid body whileminimizing collateral damage to a carotid artery by placement of anchemical ablation agent into extra-vascular space in close or immediateproximity of the carotid body; accessing extra-vascular space invicinity of a carotid body from within a carotid artery using a needledevice with a caliber that is known to be safe for arterial puncture;creating a larger ablation zone in relation to probe size using chemicalablation agent compared to RF energy; avoiding disruption of plaque, andeliminate plaque as an obstacle to carotid body ablation; and theelectrode can be used to facilitate direct electrical stimulation orblockade of carotid body function, or to sense carotid body afferentsignals as a measure of technical success of ablation.

An interstitial chemical ablation needle may be used to deliver anablative agent (also referred to herein as an ablation agent),sclerosing agent or a neural disruptive agent into a target tissue. Anexample of an agent that may be used to disable sympathetic signalingfrom a carotid body is Guanethidine, which is known to causesympathectomy, by inhibiting mitochondrial respiration, and induce animmune response.

As set forth above, an aspect of the disclosure is a method of ablatingtarget tissue within a carotid septum of a patient. In some embodimentsof this aspect ablating the target tissue includes performing anendovascular transmural carotid body ablation.

Transmural Ablation:

In general, transmural ablation as used herein refers to delivering anablation agent from an ablation element, through a vessel wall andpossibly other tissue, and to target ablation tissue to ablate thetarget tissue. An ablation element may be, for example, a radiofrequencyelectrode, a laser fiber, a microwave antenna, an ultrasound transducer,a cryoablation element, an electroporation electrode. The ablationelement may be made from radiopaque material or comprise a radiopaquemarker and it may be visualized using fluoroscopy to confirm position.Alternatively, a contrast solution may be injected through a lumen inthe ablation element to verify position. Ablation energy may bedelivered, for example from a source external to the patient such as agenerator or console, to the ablation element and through the vesselwall and other tissue to the target ablation site.

Ablation Sheath

FIG. 24A and FIG. 24B depict the distal end of an exemplary carotidaccess sheath 13 adapted for endovascular transmural ablation of acarotid body, which may be referred herein as an ETA Carotid AccessSheath. Sheath 13 comprises a central lumen 14 that traverses the lengthof the sheath from the distal end depicted in FIGS. 24A and 24B to theproximal end not shown. The central lumen is sized for use with anendovascular transmural ablation catheter, not shown, with a functionalsheath diameter between 3 French and 12 French (e.g., about 6 French).Sheath 13 comprises a distal tip 15, a deflectable segment 16 proximalto the distal tip 15, and a non-deflectable segment 17 proximal to thedeflectable segment 16. In addition, not shown, is a handle mounted atthe proximal end of the catheter with an actuator configured foruser-actuated deflection of the deflectable segment 16. A pull wire incommunication between the distal tip 15 and the handle mounted actuatoris configured to deflect the deflectable segment 16 in response to useractuation. The techniques for constructing a deflectable tipped sheathare known. Sheath 13 is adapted for endovascular transmural ablation ofa carotid body in at least one of the following manners: the radius ofcurvature 18 and length 19 of the deflectable segment are configured foruse in the vicinity of the carotid bifurcation with the radius ofcurvature 18 being between 5 mm and 20 mm, and the length of thedeflectable segment 19 being between 10 mm and 25 mm. Additionally,distal tip 15 may comprise at least one electrode, not shown, configuredfor at least one of the following: transmural ablation of a carotidbody, stimulation of a carotid body, blockade of a carotid body,stimulation of nervous function not associated with a carotid body, andblockade of nervous function not associated with the function of acarotid body. Central lumen 14 can be used to place into the region ofthe carotid bifurcation 4 an additional procedural instrument. Astimulation or blockade step can be used to locate a preferred positionfor transmural ablation of a carotid artery. Stimulation or blockade ofnervous function not associated with a carotid body can be used to avoiddamage to vital nervous structures such as a vagal nerve.

FIG. 25 depicts the distal end of an arrangement of a sheath 1100configured for transmural ablation of a carotid body. The distalablation tip 20 comprises an electrode 21, a central lumen 22, atemperature sensor 23 mounted within the wall of the distal ablation tip20 in the vicinity of the electrode 21, and a coating of electricallyisolative material 24 disposed on the distal ablation tip 20 thatdefines the electrode surface 21 by its absence, as shown. The electrode21 comprises a radial segment of the distal ablation tip between about30 degrees and 180 degrees. The axial length of the electrode 21 isbetween about 4 mm and 8 mm. Proximal to the distal ablation tip 20 is adeflectable segment 16, as well as the following features not shown butdescribed in the previous section: non-deflectable segment, handle,deflection actuator, and pull wire. The distal ablation tip isconstructed of a biocompatible and radiopaque metal such as stainlesssteel or platinum. It has an outer diameter between 6 French and 12French, an inner diameter between 5 French and 10 French defining thedistal end of the sheath's central lumen 22, and a length between 5 mmand 10 mm. The distal ablation tip 20 also has a means for attaching apull wire to the proximal end of the ablation tip 20, and a means formounting a temperature sensor 23 within the wall of the ablation tip 20,and a means for attaching an electrical conductor, not shown to thedistal tip. In addition to the features described in the in previoussection, this arrangement of sheath 1100 comprises a means to connectthe ablation tip 20, and the temperature sensor 23 to a source ofablation energy by means of an electrical connector mounted, not shown,in the vicinity of the handle, and electrical conductors, not shown,mounted in the wall of the sheath, in communication between the ablationtip 20, temperature sensor 23, and the electrical connector. In analternate embodiment the sheath may comprise two electrodes disposed ondistal tip 20 configured for bipolar RF ablation.

FIG. 26 depicts the distal end of an optional arrangement of a sheath1101, where the ablation electrode 21 is associated with the pull wire25, shown in phantom, such that the electrode surface 21 is central tothe radial position of the pull wire, and therefore the direction of theactuated deflection. This arrangement provides the user with a means todetermine the position of the electrode within a carotid artery byfluoroscopically observing the direction of the deflection using thedistal ablation tip, and the at least two radiopaque markers 26 mountedon the deflectable section 16 as visual references. In an alternativearrangement, the radiopaque markers 26 are also configured as electrodesfor electrical nervous stimulation or blockade, more generally referredto as electrical neuro-modulation. In this arrangement, a means forconnecting the at least two radiopaque electrodes 26 to a source ofstimulation or blockade energy comprises electrical conductors incommunication with the radiopaque electrodes 26, and an electricalconnector mounted in the vicinity of the handle configured forconnection to a source of stimulation or blockade energy.

FIG. 27 depicts sheath 1101 from FIG. 26 in position for ablation of acarotid body 27 and illustrates the ablation agent delivered into thecarotid septum. As depicted, the distal ablation tip electrode 21 hasbeen radially oriented in the direction of the carotid body 27 by theuser using fluoroscopic guidance with the distal tip 20 and the proximalradiopaque markers 26 serving a visual reference of the direction of anactuated deflection 28. In this depiction the carotid body 27 liesbetween the external carotid artery 29 and the internal carotid artery30 just cranial to the carotid bifurcation 31. Since the location of acarotid body 27 within the region of a carotid bifurcation 31substantially varies from patient to patient and from left side to rightside in a single patient, and since the location of the carotidbifurcation is not determinable by fluoroscopic imaging techniques, theposition and size of the carotid body is predetermined by other imagingmodalities prior to positioning the sheath into the position shown inFIG. 27. The predetermined position and size of the carotid bodyprovides the user with information necessary to select ablationparameters such that the zone of ablative effect 32 is substantiallylimited to the periarterial space comprising the carotid body 27. Theuser selectable ablation parameters for ablation with the sheath areradiofrequency power, electrode 21 temperature, duration of ablationactivation and force of contact between the distal tip 21 and the wallof the external carotid artery 29 in this depiction. Note, that the usermay also ablate the carotid body 27 from the internal carotid artery 30,or by placing the distal tip electrode 21 against the carotidbifurcation 31. In addition, if the anatomical circumstances of thepatient dictate, carotid body 27 may be ablated by sheath 1101 fromwithin an internal jugular vein 173 associated with a carotid body.

Distal Protection

FIG. 28 depicts an embodiment showing a distal end of sheath 1101 with adistal embolic protection device (“DEPD”) catheter 33 extending withincentral lumen 14 of sheath 1101. DEPD catheter 33 comprises a cathetershaft 34, with a central lumen 38 configured for use with a guide wire,not shown, an occlusion balloon 36 mounted in the vicinity of the distalend, at least one aspiration/irrigation fenestration 37 proximal to theocclusion balloon 36 and radiopaque markers 38 mounted within balloon36, a balloon inflation port 39 in communication with a ballooninflation lumen, not shown, and a distal guide wire valve 40. The DEPDcatheter shaft 34 may comprise at least a central lumen 38 and a ballooninflation lumen not shown. The central lumen 38 traverses the length ofthe DEPD catheter shaft 34 and is sized for use with a guide wirebetween 0.014″ and 0.038″ diameter. The central lumen 38 terminates at aproximal end, not shown with a female leur connection, or alternativelya Touy Borst connector. At the distal end of the catheter shaft 34proximal to the occlusion balloon 36 is at least oneaspiration/irrigation fenestration 37 in communication with the centrallumen 38. At the distal end of the catheter shaft 34 distal to theocclusion balloon is a valve, not shown mounted in the central lumen 38.The valve is configured as a septum that fluidically isolates thecentral lumen 38 from blood surrounding the distal catheter shaft 34when a guide wire is absent, but allows a guide wire to extend beyondthe distal end of catheter shaft 34 when needed for guidance. Thisallows for the removal of the guide wire from the DEPD catheter 33 sothat the central lumen 38 can then be dedicated for irrigation oraspiration of the proximal internal carotid artery 30 through thefenestration(s) 37.

FIG. 29 depicts sheath 1101 from FIG. 28 in position for ablation of acarotid body 27 and illustrates an ablation agent delivered to targettissue within the carotid septum immediately following an ablation. Asdepicted, the distal ablation tip electrode 21, residing in the internalcarotid artery 30, has been radially oriented in the direction of thecarotid body 27 by the user using fluoroscopic guidance with distal tip20 and the proximal radiopaque markers 26 serving a visual reference ofthe direction of an actuated deflection 28. In addition DEPD catheter 33is shown placed in the distal internal carotid artery 35 through thecentral lumen 14 of the sheath 1101. In this embodiment, the carotidbody 27 is ablated with sheath 1101 while the brain is protected fromembolic debris with the use of a DEPD catheter 33. An exemplary methodof ablating the carotid body includes first determining the position andsize of a target carotid body 27. The distal end of DEPD catheter 33 isthen positioned into the distal internal carotid artery 35 associatedwith the carotid body 27 as shown using a guide wire and fluoroscopicimaging for guidance. The occlusion balloon 36 is then inflated usingthe balloon inflation means of the DEPD catheter 33. Sheath 1101 isadvanced over the DEPD catheter shaft 34 into position in the proximalinternal carotid artery 30 adjacent to the determined location of thecarotid body 27. Using a combination of axial movement, rotationalmovement, and distal tip 20 deflection, the ablation electrode 21 ispositioned against the wall of the internal carotid artery 30 at alocation based at least in part on the determination of location andsize of the carotid body 27. The ablation parameters are then selected,and the ablation is initiated. Next, either the proximal carotid artery30 is irrigated with a physiological solution such as saline causing anydebris resulting from the ablation trapped proximal to the occlusionballoon 36 to flow in a retrograde fashion from the proximal internalcarotid artery 30 into and downstream in the external carotid artery 29thereby preventing the debris from entering the patient's brain, or theproximal carotid artery 30 is aspirated, thereby removing any debrisresulting from the ablation from the patient's body thereby preventingthe debris from entering the patient's brain. The ablation is thenceased and sheath 1101 is withdrawn. The occlusion balloon 36 isdeflated and the DEPD catheter 33 is withdrawn. Not all of the previoussteps need to be performed, and the order of some steps can be changedas desired.

Bifurcation Coupling Guide Wires

FIG. 30 depicts the distal end of carotid access sheath 1 withtransmural ablation catheter 44 disposed within lumen 41 of sheath 1 andextending distally therefrom. Catheter 44 comprises two side exitingguide wire ports 42 and 43 (although catheter 44 may include more thantwo) and will herein be referred to as a 2-Wire catheter 44. The 2-Wirecatheter includes an ablation element 45 mounted in the vicinity of thedistal end. The two side exiting guide wire ports 43 and 42 are insubstantial diametric opposition to each other in the vicinity of thedistal end. Catheter 44 includes catheter shaft 46 comprising at leasttwo guide wire lumens, not shown, in communication with guide wire ports43 & 44, a connection that connects the ablation element 45 to anablation energy source in the vicinity of the proximal end, not shown,and one or more guide wire fittings (not shown) for inserting a guidewire into the guide wire lumens at the proximal end, such as female leurfittings or Tuohy Borst fittings. The 2-Wire catheter is shown withfirst and second guide wires 47 exiting guide wire ports 42 and 43.Guide wire ports 42 and 43 may be configured such that guide wires 47exit the guide wire ports 42 and 43 at an angle of approximately 45degrees relative to each other as shown, or may be configured for aguide wire exit angle that is greater than or less than that depicted(e.g., between about 15 and 45 degrees). The guide wire port 42 and 43and corresponding lumens may be configured for use with guide wire 47between, for example, 0.014″ and 0.018″ diameter. The distance of theguide wire ports from the distal tip 49 may be fixed as depicted, or maybe user selectable by a distance selection means, not shown. Thedistance between guide wire port 42 and the distal tip 49 may be thesame or different than the distance between guide wire port 43 anddistal tip 49. The distance between distal tip 49 and either of guidewire port 42 and 43 may be independently selectable by the user. Theablation element 45 may be configured as at least one radiofrequencyablation electrode, which may be associated with at least onetemperature sensor, not shown. Ablation element 45 may be configured formonopolar or bipolar RF ablation. The ablation element may also beconfigured for cryo-ablation, and may be associated with at least onetemperature sensor. Catheter shaft 46 may comprise at least one cathetershaft electrode 48 configured for electrical neuro-modulation. Theablation element 45 may be configured for electrical neuro-modulationindependently or in conjunction with catheter shaft electrode(s) 40. The2-Wire catheter 44 is configured for use with a carotid access sheathhaving a working length between about 100 cm and about 140 cm, and adiameter of 5 French to 8 French. The techniques for constructing the2-Wire catheter as depicted are familiar to those skilled in the art ofcatheter making, and therefore are not further elaborated.

FIG. 31 depicts the distal end of carotid access sheath 1 with catheter51 extending within lumen 41 of sheath and extending distally therefrom.Catheter 51 comprises a single side exiting guide wire port 50 and isherein referred to as a side-wire catheter 51. Port 50 extends fromcentral lumen 41 of carotid access sheath 1. Catheter 51 comprises anablation element 54 mounted in the vicinity of the distal end, and aside exiting guide wire port 50 in the vicinity of the distal end.Catheter 51 includes catheter shaft 52 comprising a guide wire lumen,not shown, in communication with guide wire port 50, a means to connectthe ablation element 54 to an ablation energy source in the vicinity ofthe proximal end, not shown, and a means for inserting a guide wire intothe guide wire lumen at the proximal end consisting of female leurfitting or Tuohy Borst fitting, not shown. Catheter 51 is shown withguide wire 47 exiting guide wire port 50. Guide wire port 50 may beconfigured such that guide wire 47 exits guide wire port 50 at an angleof approximately 45 degrees with respect to catheter shaft 52 as shown,or may be configured for a guide wire 47 exit angle that is greater thanor less than that depicted (e.g., between about 15 and 45 degrees).Guide wire port 50 and corresponding lumen may be configured for usewith a guide wire between 0.014″ and 0.018″ diameter. The distance ofthe guide wire port 50 from the distal tip 53 may be fixed as depicted,or may be user selectable by a distance selection means, not shown.Ablation element 54 may be configured as at least one radiofrequencyablation electrode, which may be associated with at least onetemperature sensor, not shown. Ablation element 54 may be configured asone electrode and proximal ablation electrode is configured as oneelectrode in a bipolar radiofrequency ablation relationship.Alternatively, ablation element 54 may also be configured forcryo-ablation, and may be associated with at least one temperaturesensor. Ablation element 54 may comprise an electrode configured forelectrical neuro-modulation. Proximal ablation electrode 55 may also beconfigured for electrical neuro-modulation independently or inconjunction ablation element 54. The catheter shaft 46 may furthercomprise at least one catheter shaft electrode 56 configured forelectrical neuro-modulation. Ablation element 54 or proximal ablationelectrode 55 may be configured for electrical neuro-modulationindependently or in conjunction with catheter shaft electrode(s) 56.Catheter 51 is configured for use with a carotid access sheath 1 havinga working length between 100 cm and 140 cm, and a diameter of 5 Frenchto 8 French. The techniques for constructing catheter 51 as shown arefamiliar to those skilled in the art of catheter making, and thereforeare not further elaborated.

FIG. 32 illustrates catheter 44 (shown in FIG. 30) in position forablation of a carotid body 27 and ablation zone 58 immediately followingan ablation. As depicted the distal tip 49 of ablation element 45 ispositioned against the bifurcation carotid bifurcation saddle 57, with aguide wire 47 exiting side guide wire port 42 into the internal carotidartery 30, and a second guide wire 47 exiting side port 43 into theexternal carotid artery 29 as shown. The guide wires 47 provide a meansfor positioning and maintaining the distal tip 49 of ablation element 45approximately centered at the bifurcation saddle 49 in a stable mannerduring ablation. The ablation zone 58 is depicted encompassing theperiarterial space comprising the carotid body 27. Also depicted is thecarotid access sheath 1 used for placement of catheter 44 into thecommon carotid artery 59.

FIG. 32 depicts catheter 51 (from FIG. 31) in position for ablation of acarotid body 27 and the ablation zone immediately following an ablation91. As depicted, ablation element 54 is positioned against the wall ofthe external carotid artery 29 at a position distal to the carotidbifurcation saddle 57, which distance 60 as shown was predeterminedprior to the placement of the catheter 51. A guide wire 47 exiting sideguide wire port 50 is positioned into the internal carotid artery 30.The guide wire 47 in conjunction with guide wire port 50 provide a meansfor positioning the ablation element 54 against the wall of the externalcarotid artery 29 at a predetermined distance 60 based on the distancebetween the distal tip 53 and the guide wire port 50. The force ofcontact between the ablation element 54 and the wall of the externalcarotid artery 29 can be influenced by the selection of the stiffness ordiameter of the guide wire 47, the angle of exit of the guide wire 47,as well as the distance between the distal tip 53 and the guide wireport 50. For example, a force of contact that distends an ablationelement into a wall of an external carotid artery about 1 to 3 mm mayfacilitate production of a suitable ablation when deliveringradiofrequency. The ablation zone 91 is depicted encompassing theperiarterial space comprising the carotid body 27. Also depicted is thecarotid access sheath 1 used for placement of catheter 51 into thecommon carotid artery. Alternatively, guide wire 47 may be positioned inexternal carotid artery 29, and ablation element 54 may be positionedinto the internal carotid artery 30, an illustration of which is notshown.

Bipolar Assembly

FIGS. 34A-34D depict an exemplary catheter 61 that includes forceps.Catheter 61 comprises forceps assembly 62, forceps sheath 63, and aproximal terminal 64. The forceps assembly 62 comprises jaw 65 and twojaw struts 66 and 67 extending therefrom (see FIG. 34C), and tube 70 towhich jaw 65 is mounted at its distal end. A first jaw pad 68 is mountedat the end of jaw strut 66, and a second jaw pad 69 mounted on the endof jaw strut 67. The forceps sheath 63 comprises a distal tip 71 and asheath shaft 72. Mounted on the proximal end of the sheath shaft 72 isproximal terminal 64 comprising handle 73, forceps actuator 74,electrical connector 75, and a hub and tube 76 in communication withtube 70. Optionally, forceps sheath 63 may be configured with a userdeflectable segment 77 (FIG. 34B) proximal to the distal tip 71, and anon-deflectable segment 78 immediately proximal to the deflectablesegment 77. Proximal terminal 64 may further comprise a deflectablesegment actuator 89 which is in communication with deflectable segment77 by means of a pull wire, not shown. The forceps assembly 62 isdisposed within forceps sheath 63 in a slidable relationship. Forcepsjaw struts 66 and 67 are constructed to be biased to an openconfiguration as depicted in FIG. 34B. When the forceps sheath 62 isadvanced forward with respect to the forceps assembly, forceps jawstruts 66 and 67 are forced towards one another by distal tip 71 ofsheath 62. When the forceps sheath 63 is fully advanced over forcepsassembly 62 the forceps pads 68 and 69 are in a closed position asdepicted in FIG. 12A. The advancement and retraction of the forcepssheath 63 over the forceps assembly 62 is controlled by actuator 74mounted in proximal terminal handle 73. The pinching force of theforceps pads on tissue is also controlled by actuator 74. Actuator 74may optionally provide means, not shown, for the user to select aforceps pad contact force, observe by means of a force gage a contactforce, or to provide the user with a tactile feedback of the contactforce. Forceps pad 68 may be configured as an electrode whereby innersurface 80 may be bare metal and outer surface 81 may be insulated.Forceps pad 68 may be configured as an electrode whereby a portion ofouter surface 81 is bare metal and where inner surface 80 is may beinsulated. Forceps pad 68 may be configured as an electrode with atemperature sensor 82 mounted within the walls of forceps pad 68.Temperature sensor lead wire(s) 83 connect temperature sensor 82 toelectrical connector 75 of proximal terminal 64 through central tube 70.Forceps pad 69 may be configured as an electrode whereby inner surface84 may be bare metal and outer surface 85 may be insulated. Forceps pad69 may be configured as an electrode whereby a portion of outer surface85 is bare metal and where inner surface 84 is may be insulated. Forcepspad 69 may be configured as an electrode with a temperature sensor 82mounted within the walls of forceps pad 69. Temperature sensor leadwire(s) 83 connect temperature sensor 82 to electrical connector 75 ofproximal terminal 64 through central tube 70. Forceps pad 68 may besolid metal, or a polymer/metal composite structure or a ceramic/metalcomposite structure. Forceps 69 may also be solid metal, or apolymer/metal composite structure or a ceramic/metal compositestructure. Forceps jaw struts 66 & 67 may be fabricated from asuper-elastic metallic alloy such as Nitinol, but may be fabricated fromanother metallic alloy, or may be a composite structure. Central tube 70may be fabricated from a super-elastic alloy, or may be constructed fromanother metallic alloy, or may be composite structure. Central tube 70is configured to work in conjunction with forceps actuator 74 a to applya tensile force on the forceps assembly 62 for advancement of forcepssheath 63 over forceps assembly 62 to close forceps, and to apply acompressive force on the forceps assembly 62 to withdraw forceps sheath63 from over forceps assembly 62 to open forceps. Central tube 70 can beconfigured as an electrical conduit between forceps pad 68 or forcepspad 69 and electrical connector 75. Alternatively, center tube 70 may beconfigured with wires to connect forceps pad 68 or forceps pad 69 toelectrical connector 75. Electrical connector 75 is configured toconnect an electrode surface on forceps pad 68 or an electrode surfaceof forceps pad 69 to one pole of an electrical generator. Electricalconnector 75 may be configured to connect an electrode surface offorceps pad 68 to one pole of an electrical generator, and to connect anelectrode surface of forceps pad 69 to the opposite pole of anelectrical generator. An electrical generator may be configured forconnection to electrical connector 75 and to supply RF ablation currentto an electrode surface on forceps pad 68 or an electrode surface onforceps pad 69. The electrical generator may be further configured toprovide an electrode surface on forceps pad 68 with neural stimulationcurrent or neural blockade current or to provide an electrode surface onforceps pad 69 with neural stimulation current or neural blockadecurrent. Forceps pads 68 and 69 may be constructed in a manner wheretheir fluoroscopic appearance is distinct to provide the user with anability to distinguish forceps pad 68 from forceps pad 69. Thetechniques for constructing the catheter 61 are familiar to thoseskilled in the art, and therefore are not further described.

FIG. 35 depicts catheter 61 in position for ablation of a carotid body27 and ablation zone 91 immediately following an ablation. Catheter 61is positioned in the vicinity of the carotid bifurcation 31 with thedistal sheath tip 71 just proximal to the carotid bifurcation 31, withforceps pad 68 positioned against the wall of the external carotidartery 29, and forceps pad 69 positioned against the wall of theinternal carotid artery 30. Forceps sheath 63 has been advanced overforceps assembly 62 to apply a squeezing force on the carotidbifurcation saddle 57 within which lies the carotid body 27. In oneembodiment depicted here, inner surface 80 of forceps pad 68 isconfigured as an electrode. In an additional embodiment, inner surface84 of forceps pad 69 is configured as an electrode. In anotherembodiment inner surface 80 of forceps pad 68 and inner surface 84 offorceps pad 69 are configured as electrodes, where inner surface 80 andinner surface 84 are connected to the same pole, or opposite poles of anelectric generator. The electrical generator may be configured to supplyRF ablation current, or neural stimulation current or neural blockadecurrent. During RF ablation the squeezing force of forceps 62 enhancesablation by compressing the bifurcation saddle 57 to reduce the distanceof the carotid body 27 from the inner surfaces 80 and 84, and tosubstantially reduce the blood flow within the bifurcation saddle, andassociated convective cooling normally associated with interstitialblood flow. In addition to the embodiment where catheter 61 isconfigured for electrical neural stimulation, the carotid body 27 may belocated by squeezing the saddle as depicted. Since the carotid body is achemoreceptor whose function is to signal hypoxia, squeezing results inischemic hypoxia within the bifurcation saddle 57, which causes thecarotid body to signal for a user detectable physiological response toischemia induced by the forceps.

FIG. 36 depicts catheter 61 in position for ablation of a carotid body27 and ablation zone 91 immediately following an ablation. Catheter 61is positioned in the vicinity of carotid bifurcation 31 with the distalsheath tip 71 just proximal to the carotid bifurcation 31 with forcepspad 68 positioned against the wall of the external carotid artery 29proximate to carotid body 27, and with forceps pad 69 against the wallof the external carotid artery 29 approximately in diametric oppositionto forceps pad 68. In this embodiment, outer surface 81 of forceps pad68 is configured as an electrode, which may be used for RF ablation,electrical neural stimulation, and electrical neural blockade. Forcepspad 69 is constructed to be fluoroscopically distinct from forceps pad68 so that the user has a substantially unambiguous indication of thelocation of forceps pads 68 and 69 within the external carotid artery 29(e.g., location along a length of the artery and rotationalspecification within the artery). Force of contact of forceps pad 68against the wall of the external carotid artery 29 may be user adjustedby the degree of advancement of the ETAF sheath 61 over the forcepsassembly 62 by the forceps actuator 74 not shown. It is noted that theETAF catheter can be used in a similar manner with the forceps pads 68 &69 positioned within the internal carotid artery 30. Carotid body 27 mayalso be ablated by ETAF catheter 61 from internal jugular vein 173 ifwarranted.

Endovascular Transmural Ablation Suction Catheter

FIG. 37 depicts the end of an endovascular transmural ablation suctioncatheter 92 extended through a steerable carotid access sheath 1. Thecatheter comprises catheter shaft 96 with a central lumen 97, a suctioncup 93 mounted on the distal end of catheter shaft 96, and a proximalterminal 100 disposed at the proximal end of catheter shaft 96. Thecatheter is configured for use through a steerable carotid access sheath1, which has a similar arrangement to the carotid access sheath depictedin FIGS. 24A and 24B. The suction cup 93 comprises a conical structurewith a tissue contact surface 113. Disposed on tissue contact surface113 is at least one electrode wire 94, and optionally at least onetemperature sensor 95. In this embodiment suction cup 93 is fabricatedfrom an elastomeric material, which may be a silicone rubber. Thediameter of suction cup 93 outer flange 1114 is between about 2 mm andabout 10 mm when in an expanded position as shown. Suction cup 93 isconfigured to collapse within catheter 92 during insertion of thecatheter through the central lumen 14 of carotid access sheath 1 anddeploy into a use position, which is the position depicted in FIG. 37.The wall thickness of the conical section of suction cup 93 is betweenabout 0.1 mm and about 0.5 mm, which may taper across the wall section.Electrode wire(s) 94 may be molded into the wall of suction cup 93 ormay be bonded to contact surface 113. Electrode 94 may be at least onewire disposed in a radial manner as shown. Electrode 94 may be at leastone wire disposed in a spiral manner, not shown. Electrode 94 maycomprise a woven or knitted wire structure. Temperature sensor 95 may bemolded into the wall of suction cup 93, or may be bonded to contactsurface 113. Wires are configured to connect electrode 94 andtemperature sensor 95 within catheter shaft 96 to a connector disposedin the vicinity of the proximal terminal 100 not shown. The centrallumen 97 is in fluidic communication between the suction cup and fluidconnector 108 disposed in the vicinity of proximal terminal 100, notshown. Catheter shaft 96 may be fabricated from a polymer material suchas Pebax or polyurethane, of may be fabricated from a superelastic metalalloy such as Nitinol. Radiopaque marker 97 provides the user with asubstantially unambiguous fluoroscopic indication of the position of thesuction cup during use. In some embodiments the working length of thecatheter is between about 100 cm and about 140 cm.

FIG. 38 depicts catheter 92 in position for ablation of a carotid body27 and immediately following an ablation 91. Suction cup 93 is shown inposition against the carotid bifurcation saddle 57 being held in placeby applying suction to the inner contact surface 113 of suction cup 93through central lumen 97. Suction maintains firm contact between thetissue and the electrode 94 while RF electrical energy is applied toelectrode 94 at a sufficient level and duration to substantially ablatecarotid body 27.

FIG. 39 depicts in schematic form an exemplary system for carotid body27 ablation using catheter 92. The system comprises catheter 92, acarotid access sheath 1, control module 110, a suction module 103, afoot switch 1112, and cable 102 that connects the ETAS catheter 92 tothe control module 110. The control module 110 comprises a source of RFablation energy, a means to control the ablation energy based on userselection of power control algorithms, and or by means of temperaturecontrol algorithms based signals from temperature sensor(s) 95, asuction module controller that responds to vacuum sensor 107, and footswitch 1112, a user interface 111 that provides the selection ofablation parameters, an indication of the status of the system, anactuator for initiating an ablation and terminating an ablation. Suctionmodule 103 may comprise a syringe 104, a syringe actuator 106, and avacuum sensor 107. An actuator (e.g., a foot switch 1112) is configuredto actuate suction by switch depression, and deactivate suction uponremoval of said depression. In an exemplary method, the system is usedas follows. Carotid access sheath 1 is inserted into a patient and thedistal end is positioned within a common carotid artery 59. The catheteris inserted into the proximal central lumen 41 of carotid access sheath1 and advanced through central lumen until the suction cup 93 extendsbeyond the carotid access sheath 1. Suction cup 93 is maneuvered usingfluoroscopic guidance into contact with the carotid bifurcation saddle57. Foot switch 1112 is depressed, thus activating suction module 103 inthe following manner: syringe actuator 106 is moved to the rightresulting in suction; vacuum pressure is continuously monitored byvacuum sensor 107; when vacuum pressure reaches a predetermined levelbetween about 10 mm Hg and about 100 mm Hg the syringe movement isstopped, and an ablation interlock is removed allowing user actuatedablation; if the vacuum pressure decays to a level below thepredetermined level, then the syringe actuator 106 is again moved to theright until the predetermined vacuum level is re-achieved. If thepredetermined level cannot be achieved initially, or re-achieved withina syringe volume displacement between about 1 cc and about 20 cc thenthe ablation interlock remains in activation, or is reactivated, and theblood removed from the patient by the suction module is reinserted backinto the patient. User interface 111 is configured to provide the userwith an indication of the status of suction module 103, as well as thestatus of the ablation interlock. Once suction is established and theablation interlock is removed the user may activate ablation usingparameters selectable through the control module 110 user interface 111.Once the ablation is complete, the suction is removed. Catheter 92, andthe carotid access sheath 1, are then withdrawn from the target area.

Control module 110 may be configured to supply electrode(s) 94 withneural stimulation energy, or neural blockade energy. The catheter mayalso be configured to work with a needle device used to access theperiarterial space of the carotid bifurcation saddle 57 for the purposesof applying ablation energy, neural stimulation energy, neural blockadeenergy, neural stimulation chemicals, neural blockade chemical, orplacement of a temperature sensor. The control module 110 may beconfigured to supply and control the function of said needle device(s).

FIG. 40 depicts a flow chart for the use of the system comprising anendovascular transmural ablation suction catheter.

FIG. 41 depicts the distal end of an embodiment of an endovasculartransmural ablation lateral suction catheter 116. Catheter 116 comprisesa catheter shaft 117, an ablation element 118 mounted in the vicinity ofthe distal end of the catheter shaft 117, a lateral suction cup 119 alsomounted in the vicinity of the distal end of the catheter shaft 117, andpartially surrounding ablation element 118 as shown, a proximalterminal, not shown, comprising an ablation connector, and a suctionconnector. Catheter shaft 117 comprises a lumen in fluidic communicationbetween the lateral suction cup 119 and the suction connector of theproximal terminal, and a conduit for an ablation agent in communicationwith ablation element 118 and the ablation connector of the proximalterminal. Catheter shaft 117 can be fabricated from a polymer suited forcatheter construction such as Pebax or polyurethane, and may comprise abraided structure within its wall to provide torsional rigidity whilemaintaining axial flexibility to aid in directional positioning oflateral suction cup 119. Ablation element 118 may be configured formonopolar or bipolar RF ablation, cryo ablation, monopolar or bipolarneural stimulation, or monopolar or bipolar neural blockade. Lateralsuction cup 119 is fabricated from an elastomer such as silicone rubberor polyurethane, and may have radiopaque markers 120 molded into a wall,or disposed upon a wall using an adhesive. The number of radiopaquemarkers 120, size, shape, and their positions provide the user with asubstantially unambiguous indication of the position of lateral suctioncup 119 within a carotid artery. Lateral suction cup 119 is bonded tothe distal end of catheter shaft 117 with the ablation element 118substantially surrounded by lateral suction cup 119 except for ablationaperture 121. Lateral suction cup 119 may comprise a suction flange 122to facilitate suction fixation to the wall of a carotid artery duringablation. Catheter 116 is configured for use through a carotid accesssheath 1 with a central lumen between 6 French and 12 French, not shown.The working length of the catheter may be about 100 cm to about 140 cm.

FIG. 42 depicts catheter 116 in position for ablation of a carotid body27 immediately following an ablation. Suction cup 119 is shown inposition against the wall of the external carotid artery proximate tocarotid body 27 being held in place by suction applied to lateralsuction cup 119 during ablation element activation. An exemplary systemfor the catheter use is depicted in FIGS. 39 and 40, and may furtherinclude a source for a cryo ablation agent and a means to control thecryo ablation agent.

Endovascular Transmural Ablation Balloon Catheter

FIGS. 43A, 43B, 43C, 43D, and 43E depict an endovascular transmuralablation balloon catheter 123. Catheter 123 comprises catheter shaft124, guide wire lumen 125, distal tip 126 comprising guide wire lumenvalve 127, ablation electrode shaft 128, balloon shaft 129, ablationelectrode 130, balloon 131, irrigation ports 132, proximal melt liner133, radiopaque marker 134, and a proximal terminal, not shown,comprising a fluid connector in communication with guide wire lumen 125,a fluid connector for inflation of balloon 131, and an electricalconnector for ablation electrode 130. Guide wire lumen 125 traverses theentire length of catheter 123 from distal tip 126, through electrodeshaft 128, through melt liner 133, and through catheter shaft 124 to thefluid connector at the proximal terminal, not shown. Electrical wirelumen 137 runs from the distal end of electrode shaft through melt liner133, Catheter shaft 124, to the electrical connector of the proximalterminal, not shown. Electrical wire lumen 137 contains wires to connectablation electrode 130, and temperature sensor 135 with the electricalconnector of the proximal terminal. Balloon inflation lumen 136 runsfrom the distal end of balloon shaft 129, through melt liner 133,catheter shaft 124 to the fluid connector configured for ballooninflation of the proximal terminal, not shown. Distal tip 126 forms aconnection between electrode shaft 128 and balloon shaft 129, andcomprises a valve 127, which functions as septum between the blood inthe outer vicinity of distal tip 126 and guide wire lumen 125 in situwhen a guide wire is absent from guide wire lumen 125, but allows foruse of a guide wire in extension past distal tip 126 for catheterguidance. Guide wire lumen valve 127 causes irrigation fluid introducedinto the guide wire lumen 125 under pressure from the fluid connector ofthe proximal terminal to exit through irrigation ports 132 which are influidic communication with guide wire lumen 125, that would otherwise,without guide wire lumen valve 127 substantially exit distal tip 126through guide wire lumen 125, instead of through irrigation ports 132.Guide wire lumen valve 127 functions to direct irrigation fluid throughirrigation ports 132 with a guide wire extended through guide wire lumenvalve 127, and with a guide wire absent. Melt liner 133 connectselectrode shaft 128 and balloon shaft 129 to catheter shaft 124 bythermal bonding technique, which preserves the continuity of guide wirelumen 125, electrical wire lumen 137, and balloon inflation lumen 136.Catheter shaft 124, distal tip 126, electrode shaft 128, balloon shaft129, and melt liner 133 are fabricated from a thermoplastic materialsuch as Pebax, or polyurethane. Ablation electrode 130 may be mounted inthe vicinity of the center of ablation electrode shaft 128 as shown.Temperature sensor 135 may be mounted on the inner surface of ablationelectrode 130. Wires connect ablation electrode 130 and temperaturesensor 135 to the electrical connector of the proximal terminal aspreviously described. Balloon 131 is fabricated from an elastomer suchas silicone rubber, and may be centrally mounted on balloon shaft 129 asshown using adhesive. The wall thickness of balloon 131 is between about0.1 mm and about 0.4 mm when the balloon is un-inflated as depicted inFIG. 43A, and may be inflated to a diameter of 4 mm to 10 mm as depictedin FIG. 43B. Alternatively, balloon 131 may be fabricated from anon-elastomeric material such as PET. Radiopaque marker 134 is mountedcentrally on balloon shaft 129 as shown. Balloon shaft 129 is configuredto bend in the opposite direction of the bend in electrode shaft 128 asshown in FIG. 43B to provide the user with a substantially unambiguousfluoroscopic indication of the position of the ablation electrode withina carotid artery using the fluoroscopic spatial relationship betweenablation electrode 130 and radiopaque marker 134.

In an alternative embodiment not shown but similar in concept to FIGS.43A and 43B, an energy delivery element is a cryogenic applicatorpositioned on a shaft in a vicinity of a distal region of anendovascular catheter and an inflatable balloon is positioned next tothe cryogenic applicator whereas in use the balloon may at leastpartially occlude a vessel and urge the cryogenic applicator intocontact with an inner wall of a vessel proximate a target ablation site.The cryogenic applicator may be metallic and may comprise an expansionchamber within it. The expansion chamber maybe in fluid communicationwith a supply lumen used to deliver a cryogen such as substantiallyliquid N₂O and an exhaust lumen. As the cryogen exits the supply lumenthrough an orifice or flow restrictor the cryogen expands into theexpansion chamber due to a lower pressure and changes phase fromsubstantially liquid to substantially gas. This phase change of thecryogen being an endothermic reaction removes thermal energy from thecryogenic applicator and tissue in thermal contact with it such as thevessel wall and target ablation site. The cryogen gas exits theexpansion chamber through the exhaust lumen under lower pressure to aproximal region of the catheter where it is released or removed, forexample to atmosphere or to a vacuum chamber. Cryogenic power andtemperature may be controlled, for example by adjusting pressure in theexpansion chamber via reducing out flow of gas from the exhaust lumen,or by controlling flow rate of cryogen through the supply lumen. Controlof cryogenic power or temperature may be used to apply a reversiblecryo-ablation, for example via slow cooling at a higher temperature, ora more permanent cryo-ablation. Reversible cryo-ablation may be used toconfirm position before permanent cryo-ablation. Confirmation maycomprise ensuring a vital nerve (e.g., vagus, sympathetic nerves,hypoglossal nerve) is not affected and that a target (e.g., carotid bodyor carotid body nerves) is affected. The balloon may be inflated with agas such as CO₂. The balloon may occlude blood flow past the cryogenicapplicator thus removing a variable that may influence thermodynamics ofthe creation of a cryo-ablation. Furthermore, by thermally insulatingthe cryogenic applicator from blood flow more cryogenic power may bedirected toward the target ablation site allowing a deeper or colderablation. Thus the balloon may improve predictability and efficacy of acryogenic ablation. Following ablation the balloon may be deflatedallowing blood flow to resume and warm the cryoapplicator and thecatheter may be removed from the patient.

FIG. 44 depicts an alternate embodiment of catheter 140 of FIGS. 43A and43B where there are two ablation electrodes 141, and 142 configured forbipolar RF ablation. As depicted, ablation electrode 141 is associatedwith temperature sensor 143, however, the bipolar catheter can beconfigured with a temperature sensor associated with each of theablation electrodes 141 and 142. The electrical connector of theproximal terminal for this embodiment is configured for bipolarablation, and may be configured for using two temperature sensors.

FIG. 45 depicts bipolar catheter 140 in position for ablation of acarotid body 27 immediately following an ablation 91. As depicted,electrode shaft 128 and ablation electrodes 141 and 142 are pressedagainst the wall of the external carotid artery 29 by balloon 131 andproximate to carotid body 27. In this depiction, a guide wire is absent.In an exemplary method, ablation of carotid body 27 is accomplishedusing bipolar catheter 140 with the following steps. Optionally, themethod includes determining a position and size of a target carotid body27 within a patient. The distal end of bipolar catheter 140 ispositioned into the external carotid artery 29 associated with carotidbody 27 as shown using a guide wire and fluoroscopic imaging usingelectrodes 141 and 142, and radiopaque marker 134 as visual references.Balloon 131 is inflated using the fluid connector of the proximalterminal. The method then optionally fluoroscopically confirms theablation electrodes are sufficiently proximate the determined positionfor ablation. The guide wire is then withdrawn. The ablation parametersare then selected. Irrigation is then initiated. Ablation is thenperformed. Irrigation is terminated. Balloon 131 is deflated, andcatheter 140 is then withdrawn from the patient.

FIGS. 46A-46D depict a distal end of an exemplary embodiment of anendovascular transmural ablation balloon catheter 144 comprising balloonmounted ablation electrode(s) 1151. Catheter 144 comprises cathetershaft 145, guide wire lumen 149, distal tip 147, balloon shaft 146,ablation electrode(s) 151, and temperature sensor 158, balloon 1150,balloon inflation port 1153, balloon inflation port 1154, radiopaquemarker 1152, and a proximal terminal, not shown, comprising a fluidconnector in communication with guide wire lumen 149 a fluid connectorin communication with fluid port 1153, a fluid connector incommunication with fluid port 1154, and an electrical connector forablation electrode 1151. Guide wire lumen 149 traverses the entirelength of catheter 144 from distal tip 147, through balloon shaft 146,and through catheter shaft 145 to the fluid connector at the proximalterminal, not shown. Electrical wire lumen 157 runs from the distal endof catheter shaft 145, to the electrical connector of the proximalterminal, not shown. Electrical wire lumen 157 contains wires to connectablation electrode 1151, and temperature sensor 158 with the electricalconnector of the proximal terminal. Balloon inflation lumen 155 runsfrom the distal end of balloon shaft 146, through catheter shaft 145 toa fluid connector configured for balloon inflation of the proximalterminal, not shown. Balloon inflation lumen 156 runs from the distalend of balloon shaft 146, through catheter shaft 145 to a second fluidconnector configured for balloon inflation of the proximal terminal, notshown. Balloon inflation port 1153 is in fluidic communication withballoon inflation lumen 155. Balloon inflation port 1154 is in fluidiccommunication with balloon inflation lumen 156. Catheter shaft 145,distal tip 147, and balloon shaft 146, are fabricated from athermoplastic material such as Pebax, or polyurethane. Balloon 1150 isfabricated from a cross linked thermoplastic such as PET. Balloon 1150is mounted on balloon shaft 146 as shown using adhesive. The wallthickness of balloon 131 is between about 0.05 mm and about 0.2 mm.Ablation electrode 1151 and temperature sensor 158 are centrally mountedon the surface of balloon 1150 as shown using an adhesive. Temperaturesensor 158 is mounted on the inner surface of ablation electrode 1151.Wires connect ablation electrode 1151 and temperature sensor 158 to theelectrical connector of the proximal terminal as previously described.Ablation electrode 1151 is between 2 mm and 6 mm wide in the radialdirection, and between 2 mm and 10 mm in the axial direction. Ablationelectrode 1151 is configured to be flexible to conform to balloon 1150.Radiopaque marker 1152 is mounted on the surface of the balloon insubstantially diametric opposition to electrode 1151. Radiopaque marker1152 is configured to be distinctly different in fluoroscopic appearancefrom electrode 1151 to provide the user with a substantially unambiguousindication of the location of electrode 1151 within a carotid arteryusing the fluoroscopic spatial relationship between ablation electrode1151 and radiopaque marker 1152. Balloon 1150 inflation comprisescirculation of fluid from inflation port 1153 through balloon 1150 andreturning through fluid port 1154. Circulation of inflation fluidprovides carotid artery wall with protective cooling. In an alternateembodiment, two or more electrodes may be disposed on the surface ofballoon 1150 configured for bipolar RF ablation.

FIG. 47 depicts the inflation means for catheter 144 in simplifiedschematic form. The pumping means comprises a pump 159, a liquidreservoir 160 comprising a sterile physiological liquid 163, a pressurerelief valve 161, a means for setting a relief pressure 162, checkvalve, and a fluid umbilical. Pump 159 may be a positive displacementpump, such as a peristaltic roller pump. The fluid pumping rate of pump159 is controllable, and the flow direction is reversible. Fluidreservoir 160 may be a container configured to hold about 0.5 liters toabout 2 liters of sterile liquid, and to maintain sterility, and may bean IV bag. Sterile liquid is a physiological liquid 163 such as salineor ringers solution. The inflation means may be integrated into controlconsole 169, or may be a separate module. Umbilical connects theinflation means to catheter 144. To inflate balloon 1150 liquid ispumped from reservoir 160 to a positive pressure by pump 159 to liquidconnector 166 of catheter 144, through balloon 1150 from liquid port1153 to liquid port 1154, then out of catheter 144 from liquid port 167,through check valve 171, pressure relief valve 161 and then back intoreservoir 160. Pressure relief valve 161 provides a settablebackpressure to cause balloon 1150 inflation, and to regulate balloon1150 inflation pressure. To deflate balloon 1150 the direction ofrotation of pump 159 is reversed, and check valve 171 closes causing anegative pressure in balloon 1150 resulting in deflation. The liquidpumping rate may be between about 10 ml to about 100 ml per minute.

FIG. 48 depicts in simplified schematic form an alternate embodiment ofendovascular transmural ablation balloon catheter 144. In thisembodiment, fluid is pumped under positive pressure through balloon1150, from liquid port 1153 to liquid port 1154 and exits ETAB catheter144 through orifice 172 proximal to balloon 1150 as shown. Orifice 172is configured to provide a positive pressure within balloon 1150 whenliquid is introduced into balloon 1150 through liquid port 1153 inflateballoon 1150, and to provide a negative pressure within balloon 1150when liquid is withdrawn from balloon 1150 through liquid port 1153 todeflate balloon 1150.

FIG. 49 depicts catheter 144 in position for ablation of carotid body 27immediately following formation of an ablation 91. As depicted electrodehas been radially oriented in the direction of carotid body 27 by theuser using fluoroscopic guidance with electrode 1151 and radiopaquemarker 1152 serving as a visual reference to the location of electrode1151 within external carotid artery 29 as shown. Catheter 144 may alsobe positioned within the internal carotid artery 30, and alternately theinternal jugular vein 173 for transmural ablation of carotid body 27,similar to the approach shown in FIGS. 61A, 61B and 61C. Circulation ofliquid within balloon 1150 may protect the wall of carotid artery 29from collateral thermal injury, or may facilitate creation of asufficiently sized ablation.

FIGS. 50Ai, 50Aii, 50Aiii, 50Aiv, illustrates an exemplary ballooncatheter configured for bipolar RF ablation of a carotid body. Thecatheter may be designed similar to the catheter shown in FIG. 46,however at least one pair of electrodes 1160 and 1161 is mounted onballoon 1150. The pair of electrodes is aligned substantially parallelto the axis of the balloon. The pair of electrodes may be connected to aRF generator in bipolar mode, that is, so that electrode 1160 is a firstpole and electrode 1161 is a second pole and RF current is passed fromone electrode, through tissue, to the other electrode. The balloon isconfigured to occlude blood flow or at least inhibit blood flow frombecoming a short circuit between the two electrodes. This arrangementallows RF energy to be directed into the vessel wall and periarterialtissue to ablate a carotid body or its nerves. The balloon 1150 mayoptionally be inflated with a circulating fluid that functions to removeheat from the electrodes so they can deliver greater energy to thetissue. FIG. 50B shows a bipolar RF balloon catheter 1159 beingdelivered from a common carotid artery 59 (e.g., via femoral arteryaccess) to an external carotid artery 29. The balloon 1150 is inflated,causing electrodes 1160 and 1161 to come into contact with the vesselwall (e.g., on a carotid septum) substantially facing a carotid body.The electrodes may be radiopaque to facilitate radiographicvisualization during placement. Contrast may be delivered to the commoncarotid artery during placement to visualize the arteries relative tothe electrodes during placement and also to confirm that blood is notflowing past the electrodes. While a balloon is being positioned it maybe in a deflated state and a user may rotate the balloon by torqueingthe proximal end of the catheter until the electrode pair issufficiently facing a target site. Optionally a balloon may be mountedwith multiple pairs of RF electrodes spaced around the diameter of theballoon, e.g., 2, 3, 4, 5, or 6 pairs of electrodes, which may reduce oreliminate the need to rotate the balloon. A user may deliver the balloonto the carotid artery and inflate it and deliver RF energy only to theelectrode pair that is positioned in the direction of the target site tobe ablated. FIG. 50C shows a bipolar RF balloon catheter 1162 deliveredretrograde, e.g., from a superficial temporal artery access to anexternal carotid artery. The catheter 1162 configured for superficialtemporal artery delivery may be much shorter (e.g., about 10 to about 30cm) and stiffer than catheter 1159 configured to be delivered from afemoral artery, and thus may be easier to rotate by rotating a proximalend of the catheter.

Endovascular Transmural Ablation Cage Catheter

FIGS. 51Ai, 51Aii, and 51B depict an endovascular transmural ablationcage catheter 174. Catheter 174 comprises cage 177, outer catheter shaft175, inner catheter shaft 176, proximal terminal 185, and distal tip178. Cage 177 comprises electrode 181 and associated temperature sensor182, at least two cage wires 180, distal cage ring 183, and proximalcage ring 184. Outer catheter shaft 175 comprises central lumen 191, andelectrical wire lumen 190. Outer catheter shaft 175 may comprise abraided wire structure within its outer wall to provide for torsionalrigidity. Outer catheter shaft 175 may be fabricated from a polymer suchas Pebax or polyurethane. Inner catheter shaft 176 comprises guide wirelumen 179 and is configured in a slidable relationship with centrallumen 191 of outer catheter shaft 175. Proximal terminal 185 compriseshandle 186, cage actuator 187, electrical connector 188, and guide wirelumen terminal 189. Distal cage ring 183 is bonded to the distal end ofinner catheter shaft 176. Proximal cage ring 184 is bonded to the distalend of outer catheter shaft 175 as shown. Cage actuator 187 controls thedistance between the distal end of inner catheter shaft 176 and distalend of outer catheter shaft 175. Cage 177 is configured such that whenthe actuator is positioned for maximum distance between the distal endson inner catheter shaft 176 and outer catheter shaft 175 cage wires arein a substantially straight configuration as shown in FIG. 51A. Cage 177is also configured such that when actuator is positioned to reduce thedistance between inner catheter shaft 176 and outer catheter shaft 175,cage wires 180 expand in a radial direction as depicted in FIG. 51B.Electrode 181 may be disposed on cage 177 as shown by adhesive, solderor by welding. The outer surface 192 of electrode 177 is metallic.Temperature sensor 182 may be disposed on outer electrode surface 192,or be disposed beneath electrode surface 192. Wires, not shown, connectelectrode 181 and temperature sensor 182 to electrical connector 188 ofproximal terminal 185 through wire lumen 190. In an alternate embodimentat least one cage wire 180 may be configured as an electrode whereby theelectrode surface is absent electrically isolative material, andremainder of cage 177 is coated with an electrically isolative material.Cage 177 may comprise any number of cage wires. Cage 177 may comprisecage wires that are axially oriented as shown, but may also comprisecage wire(s) in a spiral configuration, in a woven configuration, or aknitted configuration. Cage wires 180 may be metallic or may benon-metallic. Cage wires 180 may be dissimilar in size, material,geometry or radiopacity. Cage 177 may comprise more than one electrodesurface, and catheter 174 may be configured for bipolar or monopolar RFablation. Catheter 174 may be configured for monopolar or bipolar neuralstimulation or neural blockade in addition to a configuration fortransmural carotid body ablation.

FIG. 52 depicts catheter 174 in position for ablation of carotid body 27immediately following formation of an ablation 91. As depicted,electrode 181 has been radially oriented in the direction of carotidbody 27 by the user using fluoroscopic guidance with electrode 1151 andopposing cage wires 180 which serve as radiopaque markers providing avisual reference to the location of electrode 181 within externalcarotid artery 29 as shown. Catheter 174 may also be positioned withinthe internal carotid artery 30, and alternately the internal jugularvein 173 for transmural ablation of carotid body 27, similar to theapproach shown in FIGS. 61A, 61B and 61C. Cage wires 180 permit bloodflow through the vessel from which it is used, providing protectivecooling the vessel wall not in contact with electrode 181.

Rearward-Looking IVUS Catheter

FIG. 53A depicts a rearward, or back, looking IVUS catheter 193 inconfiguration for use with carotid access sheath 13. FIG. 53B depictscatheter 193 in sectional view. Catheter 193 comprises sheath 195,imaging shaft 196, and proximal terminal 1200. Sheath 195 comprises acentral lumen 204 with priming valve 202 in the vicinity of the distaltip, and proximal terminal 1200 in the vicinity of the proximal end.Fluid connector 1201 is in fluidic communication with central lumen 204.Imaging shaft 196 comprises a drive shaft 203 imaging crystal housing197 at the distal end of drive shaft 203, a commutator coupling 199mounted at the proximal end of drive shaft 203, and an electricalconnection between imaging crystal housing 197 and commutator coupling199. Commutator coupling 199 is configured for use with an IVUS imagingconsole, not shown. Imaging crystal housing 197 comprises apiezoelectric crystal 198 configured for imaging in a frequency rangebetween 20 mHz and 100 mHz, (e.g., in the range 40 mHz to 50 mHZ).Crystal housing 197 is configured to orient piezoelectric crystal 198 atimaging angle 205. Imaging angle 205 is between 15 degrees and 50degrees, (e.g., at an angle between 30 and 45 degrees). Prior to use,central lumen 204 is filled with a saline solution though fluidconnector 1201 under pressure, forcing air to exit central lumen 204through valve 202. The saline provides an acoustic coupling betweenpiezoelectric crystal 198 and the wall of sheath 195. The techniques forconstructing catheter 193 as depicted are familiar to those skilled inthe art ultrasound imaging catheters, and therefore are not furtherelaborated.

FIG. 54 depicts carotid access sheath 13 in position for ablation ofcarotid body 27 immediate following formation of an ablation 91, andcatheter 193 in position for imaging ablation 91 in real time. Catheter193 allows the user to image and identify anatomical structuresassociated with carotid body 27, the location of carotid body 27, andthe size of carotid body 27. Catheter 193 may also allow the user toimage and identify vital anatomical structures that are not associatedwith carotid body 27 whose function may be preserved. Catheter 193further allows the user to image and monitor the formation of ablationlesion 91 in real time, which provides the user the ability to terminateablation in the event of encroachment of the ablative lesion into thevicinity of vital anatomical structures not associated with carotid body27. Information obtained by catheter imaging may be used to selectablation parameters. The ability of catheter 193 to image an ablationlesion is a function of the imaging frequency, and power, and the changein tissue characteristics due to ablation. Carotid access sheath 13 andcatheter 193 may also be positioned within the internal carotid artery30, and alternately the internal jugular vein 173 for transmuralablation of carotid body 27, similar to the approach shown in FIGS. 61A,61B and 61C.

Endovascular Transmural Ablation Cooled Tip Catheter

FIG. 55A depicts an endovascular transmural ablation cooled tip catheter1206. FIG. 55B depicts the distal end of catheter 1206 in exploded view.Catheter 1206 comprises ablation electrode 207, catheter shaft 206, andproximal terminal 208. Ablation electrode 207 comprises electrode cap219, heat exchanger 1214, temperature sensor 213 mounted in heatexchanger 1214, electrical conductor 218 in electrical communicationwith heat exchanger 1214 and electrode coupling sleeve 221. Cathetershaft 211 comprises a central lumen, a core extrusion 1216, and abraided overlay 1215. Proximal terminal 208 comprises electricalconnector 209, and fluid connector 1210. Temperature sensor wires 222and electrical conductor 218 connect ablation electrode 207 toelectrical connector 209. Electrode cap 219 is in electricalcommunication with heat exchanger 1214. Fluid ports 1212 depicted in thevicinity of ablation electrode 207 distal tip 220 is in fluidiccommunication with heat exchanger 1214, central lumen 217, and fluidconnector 1210. Catheter 1206 is configured for active cooling ofablation electrode 207 during ablation to prevent tissue in contact withablation electrode 207 from overheating to allow for a higher ablationpower, and therefore a larger ablation lesion than is possible withoutsaid cooling. As depicted a physiological liquid such as saline liquidis pumped through catheter from fluid connector 1210 to fluid ports 1212at a rate of between about 5 ml per minute to about 100 ml per minute bya pump, not shown, or by a syringe. The heat exchanger 1214 isconfigured transfer heat from electrode cap 219 into the physiologicalliquid in an efficient manner using spiral flow channels 223. As analternate configuration fluid ports 1212 could be replaced by havingelectrode cap 219 as a porous structure where the liquid exitingablation electrode 207 is substantially distributed over the surface ofablation electrode 207 surface. Heat exchanger 1214 and electrode cap219 are fabricated from metallic material. Catheter shaft 211 issubstantially fabricated from a polymeric material such as Pebax, orpolyurethane. Catheter 1206 can be configured to work through asteerable carotid assess sheath, or may incorporate steerablecapabilities.

FIG. 56 depicts a steerable configuration of catheter 206 in positionfor ablation of carotid body 27 immediate following an ablation 91. Asdepicted electrode 207 has been positioned against the wall of carotidartery 29 immediately adjacent to carotid body 27 by the user usingfluoroscopic guidance and the steering capability of catheter 206comprising deflectable distal segment 225, and non-deflectable segment226. Cooling saline 224 is depicted exiting liquid ports 1212. Catheter1206 may also be positioned within the internal carotid artery 30, andalternately the internal jugular vein 173 for transmural ablation ofcarotid body 27, similar to the approach shown in FIGS. 61A, 61B and61C.

Endovascular Transmural Cryo Ablation Catheter

FIG. 57A depicts in simplified schematic form an endovascular transmuralcryo ablation catheter 227. FIG. 57B depicts in cross section view acatheter 227. Catheter 227 comprises cryo-ablation element 228, cathetershaft 229, proximal terminal 230, and optional neural modulationelectrodes 233. Proximal terminal 230 comprises electrical connector231, cryogen connector 232, and gas exhaust port 242. Cryo-ablationelement 228 comprises cryo cap 234, heat exchanger 236, capillary tube237, and temperature sensor 238. Cryo cap 234 is a thin walled metallicstructure with high thermal conductivity. Heat exchanger 236 is a porousmetallic structure with high thermal conductivity and is disposed withincryo cap 234 in an intimate heat transfer relationship. Heat exchanger236 may be fabricated using a sintering process of a metal with highthermal conductivity such as copper. Capillary tube 237 is configured tometer the flow of cryogen from cryogen supply tube 240 into expansionchamber 235 at a predetermined rate. Capillary tube 237 may befabricated from a stainless steel hypodermic tube. Temperature sensor238 is disposed in the vicinity of heat exchanger 236. Cryogen supplytube 240 is bonded by adhesive to capillary tube 238 as shown. Ablationelement 228 is bonded to the distal end of catheter shaft 229. Cathetershaft 229 comprises a central lumen 241, and may be fabricated from apolymer such as Pebax or polyurethane, with an outer diameter between 5French and 12 French. The working length of catheter 227 is between 90cm and 140 cm. Cryogen supply tube 240 is configured for delivery of acryogen under high pressure on the order of about 500 psi to about 2000psi. Cryogen supply tube may be fabricated from a polymer, or from asuper elastic metal alloy such as Nitinol. Cryogen supply tube 240 is influidic communication with cryogen connector 232. Central lumen 241 isin fluidic communication with exhaust port 242. Electrical cable 239connects temperature sensor 238, and neural modulation electrodes 233 toelectrical connector 231.

FIG. 58A depicts the distal end of catheter 227 in working configurationwith steerable carotid access sheath 1. FIG. 58B depicts an alternateembodiment of catheter 243 with steering capability comprising a userdeflectable segment 245 and a non-deflectable segment 246 proximal todeflectable segment 245. Deflectable segment 245 is actuated by a pullwire, and a deflection actuator disposed on a handle of proximalterminal, not shown. An ice ball 244 is depicted to represent acryo-ablation functional modality.

FIG. 59 depicts in simplified schematic form an exemplary endovasculartransmural cryo ablation system. The system comprises catheter 227,control console 249, cryogen source 250, electrical umbilical 247,cryogen umbilical 248, and cryogen supply line 251. Control console 249has a user interface 252 that provides the user with a means to selectcryo-ablation parameters, activate and deactivate a cryo-ablation, andto monitor the progress of a cryo-ablation. In addition, control console249 may have second user interface 253 that allows the user to selectelectrical neuro-modulation parameters, activate neuro-modulation,deactivate neuro-modulation, and to monitor neuro-modulation. Controlconsole 249 comprises a means to control flow of cryogen from cryogensource 250 to catheter 227 according to user settings of user interface252.

In an exemplary method of use (with reference to FIGS. 57A, 57B, and59), ablation element 228 receives cryogen under high pressure fromcontrol console 249, cryogen umbilical 248, cryogen connector 232, andcryogen supply tube 240. Cryogen under high pressure enters low pressureexpansion chamber 235 resulting in a drop in temperature dependent onthe cryogen used, the pressure of the cryogen prior to expansion, andthe expanded pressure. The expanded cryogen flows through heat exchanger236, which transfers heat from ablation cap surface into the cryogenflowing through heat exchanger 236. Temperature sensor 238 is used bythe control console to control the flow the cryogen from the controlconsole 249 to catheter 227 by means of flow or pressure modulation. Thecryogen exits heat exchanger 236 into central lumen 241 and out exhaustport 242. Cryogen may be supplied to cryo-ablation element 228 in theform of a liquid such liquid nitrogen, or liquid carbon dioxideresulting in part in an evaporative cooling process, or the cryogen maybe supplied to 228 in the form of a gas such as argon, nitrogen, orcarbon dioxide where the cooling process is by Joule-Thompson effect(adiabatic expansion). The surface temperature of a cryo-ablationelement may be controlled by control console 249 at a temperaturebetween −20 degrees centigrade and −120 degrees centigrade duringablation by controlling the flow rate, or pressure of the cryogen.

FIG. 60 depicts a steerable configuration of catheter 243 in positionfor cryo-ablation of carotid body 27 immediately following an ablation91. As depicted cryo-ablation element 228 has been placed against thewall of external carotid artery 29 adjacent to carotid body 27 by theuser using fluoroscopic guidance and the steering capability of catheter243 comprising deflectable distal segment 245, and non-deflectablesegment 246. Catheter 243 may alternatively be positioned within theinternal carotid artery 30, or the internal jugular vein 173 fortransmural cryo-ablation of carotid body 27, similar to the approachshown in FIGS. 61A, 61B and 61C.

FIG. 61A depicts in simplified schematic form the placement of a carotidbody ablation catheter 650 into a patient via an endovascular approachwith a femoral vein puncture. The distal end of the catheter 651 isdepicted in the left internal jugular vein 173 at the level of a carotidseptum containing a target carotid body 101, positioned to deliverablative energy to a carotid body or its nerves. As depicted thecatheter 650 is inserted into the patient at an insertion site in thevicinity of the groin into a femoral vein and advanced through theinferior vena cava, superior vena cava, left common jugular vein andinto the left internal jugular vein 173. Alternatively, the insertionsite may be selected to gain venous access through a brachial vein, asub-clavian vein, a common jugular vein 53, or any suitable peripheralvein. Furthermore, the distal end of the catheter 650 may be positionedfor carotid body ablation in a different vein that proximate to a targetablation site, such as a facial vein (not shown) depending on theparticular vascular and neural anatomy of the patient.

In some patients an internal jugular vein 173 is positioned touching orwithin about 5 mm of a target carotid body 27 as shown in FIG. 61B. Insuch a scenario a carotid body ablation catheter 650 may be advancedinto the internal jugular vein 173 and an ablation element 228 may beplaced to deliver ablation energy to the target carotid body 27.

In some patients an internal jugular vein 173 is positioned greater thanabout 5 mm from a target carotid body 27 as shown in FIG. 61C. In such ascenario the internal jugular vein 173, which is relatively pliable, maybe maneuvered closer to the target carotid body 27 by applying adeflection force to a catheter 650 in the vein. Once close enough to thetarget site an ablation element 651 on a distal end of the catheter 650may deliver ablative energy.

An angiographic catheter may be positioned in a common carotid artery 59for the purpose creating an arterial angiographic image of the region ofthe carotid arteries 59, 30 and 29 for the purpose of guiding atrans-venous ablation catheter. An angiographic catheter may be insertedinto a femoral artery through an insertion site in the groin, thenadvanced through the abdominal aorta, the aortic arch, and into the leftcommon carotid artery 59 using standard angiographic techniques. Itwould be understood to those skilled in the art of endovascularinterventions that means other than carotid artery angiography can beused to guide trans-venous carotid body ablation. For example,extracorporeal ultrasonic imaging of the neck may be used, as well asintra-vascular ultrasound, computed tomography angiography, and otherknown modalities alone or in combination.

Deployable Helical Structure

As shown in FIG. 62, a carotid body ablation catheter may comprise adeployable helical structure 1240 with at least one ablation electrode1241 mounted to the helix. The helix may comprise an elastic orsuperelastic structural member such as Nitinol that allows the helix toresiliently conform to an undeployed state when contained in a deliverysheath 1242 and deploy to a helical configuration when advanced from thesheath 1242. The helical structure functions to provide stability andcontact force of the electrode 1241 with the vessel wall 1243. Thehelical structure 1240 may have a preformed shape with a diameter ofabout 6 mm, which may allow it to expand in vessel such as an externalcarotid artery 206 having a diameter of about 4 to 6 mm and apply anoutward force on the vessel wall 1243. The preformed shape may comprisea first helix 1244 proximal the electrode and a second helix 1245 distalthe electrode with an electrode mounting section that is substantiallyparallel to the axis of the helical structure, or the axis of thevessel. The electrode mounting section may be about 4 to about 8 mm longfor mounting an about 4 to about 8 mm long cylindrical electrode with adiameter between about 1 and about 3 mm. Alternatively, the preformedshape may comprise a single helix and an electrode may have asubstantially spherical shape with a diameter of about 1 to about 3 mm.The catheter may comprise a single electrode, in which case the helicalstructure may require rotation to align the electrode with the targetablation site. Alternatively, the catheter may comprise multipleelectrodes (e.g., 2, 3, 4, 5, or more, electrodes) and the electrodethat is best aligned with a target ablation site may be activated.

FIG. 63 illustrates an embodiment of a carotid body ablation catheterthat comprises an expandable loop 1250 with an electrode 1251 mounted tothe loop. The loop may have an adjustable radius that is controlled by apull wire connected to an actuator in a handle (not shown).Alternatively, the loop may be self-expanding, comprising an elasticmember such as Nitinol that is adapted to deploy when advanced distallyfrom a sheath. The loop functions to stabilize and provide contact forceof an electrode 1251 mounted to the loop, with a wall of an externalcarotid artery 206. The loop may be configured to expand to a diameterof about 6 mm. The electrode 1251 may be cylindrical, for example,having a length of about 4 to about 8 mm and a diameter of about 1 toabout 3 mm. Alternatively, the electrode may be spherical with adiameter of about 1 to about 3 mm. A user-controlled loop radius maybeneficially allow the user to deploy the loop to a diameter less thanthe vessel diameter, rotate the loop to align the electrode with atarget ablation site, then further expand the loop to apply contactforce between the electrode and vessel wall. The catheter may optionallycomprise a lumen 1253 in which a guide wire can be positioned such thatthe catheter can be delivered over a guide wire 1252.

Methods of Therapy:

In some embodiments an embolism protection device or system is alsopositioned within the patient's vasculature. There may be danger ofcreating a brain embolism while performing an endovascular procedure ina patient's carotid artery, for example, a thrombus may be created bydelivering ablation energy such as on a radiofrequency electrode, or apiece of atheromatous plaque may be dislodged by catheter movement. Inaddition to a carotid body ablation catheter, an endovascular cathetermay be used to place a brain embolism protection device in a patient'sinternal carotid artery during a carotid body ablation procedure. Thetreatment may include occluding a patient's internal carotid artery.Blood flowing from a common carotid artery 102 would not flow through aconnecting internal carotid artery 201, which feeds the brain, butinstead would flow through the external carotid artery, which feedsother structures of the head that are much more capable of safelyreceiving an embolism. For example, a brain embolism protection device610 in the form of an inflatable balloon is placed in an internalcarotid artery 201. The balloon may be made from a soft, stretchable,compliant balloon material such as silicone and may be inflated with afluid (e.g., saline or contrast agent) through an inflation lumen. Theinflation fluid may be injected into an inlet port by a syringe or by acomputer controlled pump system. The balloon may be placed, using adelivery sheath, in an internal carotid artery (e.g., up to about 10 cmfrom a carotid bifurcation). Contrast solution may be injected into thecommon carotid artery 102, for example through the delivery sheath toallow radiographic visualization of the common 102, internal 201 andexternal 206 carotid arteries, which may assist a physician to positiona brain embolism protection device 610. An endovascular ablationcatheter may place an energy delivery element proximate a carotid body,for example in a carotid body. It is expected that blood flow wouldcarry any debris into the external carotid artery where it is harmless.Occlusion of an internal carotid artery may be done for a period of timethat allows an ablation procedure and that is safe for the brain (e.g.,less than or equal to about 3 minutes, or between about 1 to 2 minutes).After the carotid body is ablated the brain embolism protection devicemay be deployed and removed from the patient or positioned on thepatient's contralateral side in the event of ablating the contralateralcarotid body.

In another embodiment a brain embolism protection device may be ablood-permeable filter deployed in a patient's internal carotid artery.A filter may be a fine mesh or net connected to a deployable frame thatexpands to envelop a cross-section of an internal carotid artery distalto a bifurcation. Other embodiments of a blood-permeable filter mayinclude wire-type expandable devices such as baskets or umbrellas. Sucha filter may allow antegrade blood flow to continue to the brain whiletrapping and retrieving debris in the blood, preventing a brainembolism. Such a device may be deployed in an internal carotid arteryprior to the placement of ablation catheter and retrieved followingablation.

A method in accordance with a particular embodiment includes ablating atleast one of a patient's carotid bodies based at least in part onidentifying the patient as having a sympathetically mediated diseasesuch as cardiac, metabolic, or pulmonary disease such as hypertension,pulmonary hypertension (e.g., refractory hypertension), congestive heartfailure (CHF), or dyspnea.

A procedure may include diagnosis, selection based on diagnosis, furtherscreening (e.g., baseline assessment of chemosensitivity), treating apatient based at least in part on diagnosis or further screening via achemoreceptor (e.g., carotid body) ablation procedure such as one of theembodiments disclosed. Additionally, following ablation a method oftherapy may involve conducting a post-ablation assessment to comparewith the baseline assessment and making decisions based on theassessment (e.g., adjustment of drug therapy, re-treat in new positionor with different parameters, or ablate a second chemoreceptor if onlyone was previously ablated).

In some embodiments carotid body ablation procedure may comprise thefollowing steps or a combination thereof: patient sedation, locating atarget peripheral chemoreceptor, visualizing a target peripheralchemoreceptor (e.g., carotid body), confirming a target ablation site isor is proximate a peripheral chemoreceptor, confirming a target ablationsite is safely distant from vital structures that are preferablyprotected (e.g., hypoglossal and vagus nerves), providing stimulation(e.g., electrical, mechanical, chemical) to a target site or targetperipheral chemoreceptor prior to, during or following an ablation step,monitoring physiological responses to said stimulation, anesthetizing atarget site, protecting the brain from potential embolism, thermallyprotecting an arterial or venous wall (e.g., carotid artery, jugularvein), ablating a target site or peripheral chemoreceptor, monitoringablation parameters (e.g., temperature, impedance, blood flow in acarotid artery), confirming a reduction of chemoreceptor activity (e.g.,chemosensitivity, HR, blood pressure, ventilation, sympathetic nerveactivity) during or following an ablation step, removing an ablationdevice, conducting a post-ablation assessment, repeating any steps ofthe chemoreceptor ablation procedure on another peripheral chemoreceptorin the patient.

Patient screening, as well as post-ablation assessment may includephysiological tests or gathering of information, for example,chemoreflex sensitivity, central sympathetic nerve activity, heart rate,heart rate variability, blood pressure, ventilation, production ofhormones, peripheral vascular resistance, blood pH, blood PCO₂, degreeof hyperventilation, peak VO₂, VE/VCO₂ slope. Directly measured maximumoxygen uptake (more correctly pVO₂ in heart failure patients) and indexof respiratory efficiency VE/VCO₂ slope has been shown to be areproducible marker of exercise tolerance in heart failure and provideobjective and additional information regarding a patient's clinicalstatus and prognosis.

A method of therapy may include electrical stimulation of a targetregion, using a stimulation electrode, to confirm proximity to a carotidbody. For example, a stimulation signal having a 1-10 milliamps (mA)pulse train at about 20 to 40 Hz with a pulse duration of 50 to 500microseconds (μs) that produces a positive carotid body stimulationeffect may indicate that the stimulation electrode is within sufficientproximity to the carotid body or nerves of the carotid body toeffectively ablate it. A positive carotid body stimulation effect couldbe increased blood pressure, heart rate, or ventilation concomitant withapplication of the stimulation. These variables could be monitored,recorded, or displayed to help assess confirmation of proximity to acarotid body. A catheter-based technique, for example, may have astimulation electrode proximal to the energy delivery element used forablation. Alternatively, the energy delivery element itself may also beused as a stimulation electrode. Alternatively, an energy deliveryelement that delivers a form of ablative energy that is not electrical,such as a cryogenic ablation applicator, may be configured to alsodeliver an electrical stimulation signal as described earlier. Yetanother alternative embodiment comprises a stimulation electrode that isdistinct from an ablation element. For example, during a surgicalprocedure a stimulation probe can be touched to a suspected carotid bodythat is surgically exposed. A positive carotid body stimulation effectcould confirm that the suspected structure is a carotid body andablation can commence. Physiological monitors (e.g., heart rate monitor,blood pressure monitor, blood flow monitor, MSNA monitor) maycommunicate with a computerized stimulation generator, which may also bean ablation generator, to provide feedback information in response tostimulation. If a physiological response correlates to a givenstimulation the computerized generator may provide an indication of apositive confirmation.

Alternatively or in addition a drug known to excite the chemo sensitivecells of the carotid body can be injected directly into the carotidartery or given systemically into a patient's vein or artery in order toelicit hemodynamic or respiratory response. Examples of drugs that mayexcite a chemoreceptor include nicotine, atropine, Doxapram, Almitrine,hyperkalemia, Theophylline, adenosine, sulfides, Lobeline,Acetylcholine, ammonium chloride, methylamine, potassium chloride,anabasine, coniine, cytosine, acetaldehyde, acetyl ester and the ethylether of 1-methylcholine, Succinylcholine, Piperidine, monophenol esterof homo-iso-muscarine and acetylsalicylamides, alkaloids of veratrum,sodium citrate, adenosinetriphosphate, dinitrophenol, caffeine,theobromine, ethyl alcohol, ether, chloroform, phenyldiguanide,sparteine, coramine (nikethamide), metrazol (pentylenetetrazol),iodomethylate of dimethylaminomethylenedioxypropane,ethyltrimethylammoniumpropane, trimethylammonium, hydroxytryptamine,papaverine, neostigmine, acidity.

A method of therapy may further comprise applying electrical or chemicalstimulation to the target area or systemically following ablation toconfirm a successful ablation. Heart rate, blood pressure or ventilationmay be monitored for change or compared to the reaction to stimulationprior to ablation to assess if the targeted carotid body was ablated.Post-ablation stimulation may be done with the same apparatus used toconduct the pre-ablation stimulation. Physiological monitors (e.g.,heart rate monitor, blood pressure monitor, blood flow monitor, MSNAmonitor) may communicate with a computerized stimulation generator,which may also be an ablation generator, to provide feedback informationin response to stimulation. If a physiological response correlated to agiven stimulation is reduced following an ablation compared to aphysiological response prior to the ablation, the computerized generatormay provide an indication ablation efficacy or possible proceduralsuggestions such as repeating an ablation, adjusting ablationparameters, changing position, ablating another carotid body orchemosensor, or concluding the procedure.

Visualization:

An optional step of visualizing internal structures (e.g., carotid bodyor surrounding structures) may be accomplished using one or morenon-invasive imaging modalities, for example fluoroscopy, radiography,arteriography, computer tomography (CT), computer tomography angiographywith contrast (CTA), magnetic resonance imaging (MRI), or sonography, orminimally invasive techniques (e.g., IVUS, endoscopy, optical coherencetomography). A visualization step may be performed as part of a patientassessment, prior to an ablation procedure to assess risks and locationof anatomical structures, during an ablation procedure to help guide anablation device, or following an ablation procedure to assess outcome(e.g., efficacy of the ablation). Visualization may be used to: (a)locate a carotid body, (b) locate vital structures that may be adverselyaffected, or (c) locate, identify and measure arterial plaque.

Endovascular (for example transfemoral) arteriography of the commoncarotid and then selective arteriography of the internal and externalcarotids may be used to determine a position of a catheter tip at acarotid bifurcation. Additionally, ostia of glomic arteries (thesearteries may be up to 4 mm long and arise directly from the main parentartery) can be identified by dragging the dye injection catheter andreleasing small amounts (“puffs”) of dye. If a glomic artery isidentified it can be cannulated by a guide wire and possibly furthercannulated by small caliber catheter. Direct injection of dye intoglomic arteries can further assist the interventionalist in the ablationprocedure. It is appreciated that the feeding glomic arteries are smalland microcatheters may be needed to cannulate them.

Alternatively, ultrasound visualization may allow a physician to see thecarotid arteries and even the carotid body. Another method forvisualization may consist of inserting a small needle (e.g., 22 Gauge)with sonography or computer tomography (CT) guidance into or toward thecarotid body. A wire or needle can be left in place as a fiducial guide,or contrast can be injected into the carotid body. Runoff of contrast tothe jugular vein may confirm that the target is achieved.

Computer Tomography (CT) and computer tomography angiography (CTA) mayalso be used to aid in identifying a carotid body. Such imaging could beused to help guide an ablation device to a carotid body.

Ultrasound visualization (e.g., sonography) is an ultrasound-basedimaging technique used for visualizing subcutaneous body structuresincluding blood vessels and surrounding tissues. Doppler ultrasound usesreflected ultrasound waves to identify and display blood flow through avessel. Operators typically use a hand-held transducer/transceiverplaced directly on a patient's skin and aimed inward directingultrasound waves through the patient's tissue. Ultrasound may be used tovisualize a patient's carotid body to help guide an ablation device.

Visualization and navigation steps may comprise multiple imagingmodalities (e.g., CT, fluoroscopy, ultrasound) superimposed digitally touse as a map for instrument positioning. Superimposing borders of greatvessels such as carotid arteries can be done to combine images.

Responses to stimulation at different coordinate points can be storeddigitally as a 3-dimensional or 2-dimensional orthogonal plane map. Suchan electric map of the carotid bifurcation showing points, or pointcoordinates that are electrically excitable such as baroreceptors,baroreceptor nerves, chemoreceptors and chemoreceptor nerves can besuperimposed with an image (e.g., CT, fluoroscopy, ultrasound) ofvessels. This can be used to guide the procedure, and identify targetareas and areas to avoid.

In addition, as noted above, it should be understood that a deviceproviding therapy can also be used to locate a carotid body as well asto provide various stimuli (electrical, chemical, other) to test abaseline response of the carotid body chemoreflex (CBC) or carotid sinusbaroreflex (CSB) and measure changes in these responses after therapy ora need for additional therapy to achieve the desired physiological andclinical effects.

Patient Selection and Assessment:

In an embodiment, a procedure may comprise assessing a patient to be aplausible candidate for carotid body ablation. Such assessment mayinvolve diagnosing a patient with a sympathetically mediated disease(e.g., MSNA microneurography, measure of cataclomines in blood or urine,heart rate, or low/high frequency analysis of heart rate variability maybe used to assess sympathetic tone). Patient assessment may furthercomprise other patient selection criteria, for example indices of highcarotid body activity (i.e., carotid body hypersensitivity orhyperactivity) such as a combination of hyperventilation and hypocarbiaat rest, high carotid body nerve activity (e.g., measured directly),incidence of periodic breathing, dyspnea, central sleep apnea elevatedbrain natriuretic peptide, low exercise capacity, having cardiacresynchronization therapy, atrial fibrillation, ejection fraction of theleft ventricle, using beta blockers or ACE inhibitors.

Patient assessment may further involve selecting patients with highperipheral chemosensitivity (e.g., a respiratory response to hypoxianormalized to the desaturation of oxygen greater than or equal to about0.7 l/min/min SpO₂), which may involve characterizing a patient'schemoreceptor sensitivity, reaction to temporarily blocking carotid bodychemoreflex, or a combination thereof.

Although there are many ways to measure chemosensitivity they can bedivided into (a) active provoked response and (b) passive monitoring.Active tests can be done by inducing intermittent hypoxia (such as bytaking breaths of nitrogen or CO₂ or combination of gases) or byrebreathing air into and from a 4 to 10 liter bag. For example: ahypersensitive response to a short period of hypoxia measured byincrease of respiration or heart rate may provide an indication fortherapy. Ablation or significant reduction of such response could beindicative of a successful procedure. Also, electrical stimulation,drugs and chemicals (e.g., dopamine, lidocane) exist that can block orexcite a carotid body when applied locally or intravenously.

The location and baseline function of the desired area of therapy(including the carotid and aortic chemoreceptors and baroreceptors andcorresponding nerves) may be determined prior to therapy by applicationof stimuli to the carotid body or other organs that would result in anexpected change in a physiological or clinical event such as an increaseor decrease in SNS activity, heart rate or blood pressure. These stimulimay also be applied after the therapy to determine the effect of thetherapy or to indicate the need for repeated application of therapy toachieve the desired physiological or clinical effect(s). The stimuli canbe either electrical or chemical in nature and can be delivered via thesame or another catheter or can be delivered separately (such asinjection of a substance through a peripheral IV to affect the CBC thatwould be expected to cause a predicted physiological or clinicaleffect).

A baseline stimulation test may be performed to select patients that maybenefit from a carotid body ablation procedure. For example, patientswith a high peripheral chemosensitivity gain (e.g., greater than orequal to about two standard deviations above an age matched generalpopulation chemosensitivity, or alternatively above a thresholdperipheral chemosensitivity to hypoxia of 0.5 or 0.7 ml/min/% O₂) may beselected for a carotid body ablation procedure. A prospective patientsuffering from a cardiac, metabolic, or pulmonary disease (e.g.,hypertension, CHF, diabetes) may be selected 700. The patient may thenbe tested to assess a baseline peripheral chemoreceptor sensitivity(e.g., minute ventilation, tidal volume, ventilator rate, heart rate, orother response to hypoxic or hypercapnic stimulus) 702. Baselineperipheral chemosensitivity may be assessed using tests known in the artwhich involve inhalation of a gas mixture having reduced O₂ content(e.g., pure nitrogen, CO₂, helium, or breathable gas mixture withreduced amounts of O₂ and increased amounts of CO₂) or rebreathing ofgas into a bag. Concurrently, the patient's minute ventilation orinitial sympathetically mediated physiologic parameter such as minuteventilation or HR may be measured and compared to the O₂ level in thegas mixture. Tests like this may elucidate indices called chemoreceptorset-point and gain. These indices are indicative of chemoreceptorsensitivity. If the patient's chemosensitivity is not assessed to behigh (e.g., less than about two standard deviations of an age matchedgeneral population chemosensitivity, or other relevant numericthreshold) then the patient may not be a suitable candidate for acarotid body ablation procedure 704. Conversely, a patient withchemoreceptor hypersensitivity (e.g., greater than or equal to about twostandard deviations above normal) may proceed to have a carotid bodyablation procedure 706. Following a carotid body ablation procedure thepatient's chemosensitivity may optionally be tested again 708 andcompared to the results of the baseline test 702. The second test 708 orthe comparison of the second test to the baseline test may provide anindication of treatment success 710 or suggest further intervention 712such as possible adjustment of drug therapy, repeating the carotid bodyablation procedure with adjusted parameters or location, or performinganother carotid body ablation procedure on a second carotid body if thefirst procedure only targeted one carotid body. It may be expected thata patient having chemoreceptor hypersensitivity or hyperactivity mayreturn to about a normal sensitivity or activity following a successfulcarotid body ablation procedure.

In an alternative protocol for selecting a patient for a carotid bodyablation, patients with high peripheral chemosensitivity or carotid bodyactivity (e.g., ≥about 2 standard deviations above normal) alone or incombination with other clinical and physiologic parameters may beparticularly good candidates for carotid body ablation therapy if theyfurther respond positively to temporary blocking of carotid bodyactivity. A prospective patient suffering from a cardiac, metabolic, orpulmonary disease may be selected 700 to be tested to assess thebaseline peripheral chemoreceptor sensitivity 702. A patient withouthigh chemosensitivity may not be a plausible candidate 704 for a carotidbody ablation procedure. A patient with a high chemosensitivity may begiven a further assessment that temporarily blocks a carotid bodychemoreflex 714. For example a temporary block may be done chemically,for example using a chemical such as intravascular dopamine ordopamine-like substances, intravascular alpha-2 adrenergic agonists,oxygen, in general alkalinity, or local or topical application ofatropine externally to the carotid body. A patient having a negativeresponse to the temporary carotid body block test (e.g., sympatheticactivity index such as respiration, HR, heart rate variability, MSNA,vasculature resistance, etc. is not significantly altered) may be a lessplausible candidate 704 for a carotid body ablation procedure.Conversely, a patient with a positive response to the temporary carotidbody block test (e.g., respiration or index of sympathetic activity isaltered significantly) may be a more plausible candidate for a carotidbody ablation procedure 716.

There are a number of potential ways to conduct a temporary carotid bodyblock test 714. Hyperoxia (e.g., higher than normal levels of PO₂) forexample, is known to partially block (about a 50%) or reduce afferentsympathetic response of the carotid body. Thus, if a patient'ssympathetic activity indexes (e.g., respiration, HR, HRV, MSNA) arereduced by hyperoxia (e.g., inhalation of higher than normal levels ofO₂) for 3-5 minutes, the patient may be a particularly plausiblecandidate for carotid body ablation therapy. A sympathetic response tohyperoxia may be achieved by monitoring minute ventilation (e.g.,reduction of more than 20-30% may indicate that a patient has carotidbody hyperactivity). To evoke a carotid body response, or compare it tocarotid body response in normoxic conditions, CO₂ above 3-4% may bemixed into the gas inspired by the patient (nitrogen content will bereduced) or another pharmacological agent can be used to invoke acarotid body response to a change of CO₂, pH or glucose concentration.Alternatively, “withdrawal of hypoxic drive” to rest state respirationin response to breathing a high concentration O₂ gas mix may be used fora simpler test.

An alternative temporary carotid body block test involves administeringa sub-anesthetic amount of anesthetic gas halothane, which is known totemporarily suppress carotid body activity. Furthermore, there areinjectable substances such as dopamine that are known to reversiblyinhibit the carotid body. However, any substance, whether inhaled,injected or delivered by another manner to the carotid body that affectscarotid body function in the desired fashion may be used.

Another alternative temporary carotid body block test involvesapplication of cryogenic energy to a carotid body (i.e., removal ofheat). For example, a carotid body or its nerves may be cooled to atemperature range between about −15° C. to 0° C. to temporarily reducenerve activity or blood flow to and from a carotid body thus reducing orinhibiting carotid body activity.

An alternative method of assessing a temporary carotid body block testmay involve measuring pulse pressure. Noninvasive pulse pressure devicessuch as Nexfin (made by BMEYE, based in Amsterdam, The Netherlands) canbe used to track beat-to-beat changes in peripheral vascular resistance.Patients with hypertension or CHF may be sensitive to temporary carotidbody blocking with oxygen or injection of a blocking drug. Theperipheral vascular resistance of such patients may be expected toreduce substantially in response to carotid body blocking. Such patientsmay be good candidates for carotid body ablation therapy.

Yet another index that may be used to assess if a patient may be a goodcandidate for carotid body ablation therapy is increase of baroreflex,or baroreceptor sensitivity, in response to carotid body blocking. It isknown that hyperactive chemosensitivity suppresses baroreflex. Ifcarotid body activity is temporarily reduced the carotid sinusbaroreflex (baroreflex sensitivity (BRS) or baroreflex gain) may beexpected to increase. Baroreflex contributes a beneficialparasympathetic component to autonomic drive. Depressed BRS is oftenassociated with an increased incidence of death and malignantventricular arrhythmias. Baroreflex is measurable using standardnon-invasive methods. One example is spectral analysis of RR interval ofECG and systolic blood pressure variability in both the high- andlow-frequency bands. An increase of baroreflex gain in response totemporary blockade of carotid body can be a good indication forpermanent therapy. Baroreflex sensitivity can also be measured by heartrate response to a transient rise in blood pressure induced by injectionof phenylephrine.

An alternative method involves using an index of glucose tolerance toselect patients and determine the results of carotid body blocking orremoval in diabetic patients. There is evidence that carotid bodyhyperactivity contributes to progression and severity of metabolicdisease.

In general, a beneficial response can be seen as an increase ofparasympathetic or decrease of sympathetic tone in the overall autonomicbalance. For example, Power Spectral Density (PSD) curves of respirationor HR can be calculated using nonparametric Fast Fourier Transformalgorithm (FFT). FFT parameters can be set to 256-64 k buffer size,Hamming window, 50% overlap, 0 to 0.5 or 0.1 to 1.0 Hz range. HR andrespiratory signals can be analyzed for the same periods of timecorresponding to (1) normal unblocked carotid body breathing and (2)breathing with blocked carotid body.

Power can be calculated for three bands: the very low frequency (VLF)between 0 and 0.04 Hz, the low frequency band (LF) between 0.04-0.15 Hzand the high frequency band (HF) between 0.15-0.4 Hz. Cumulativespectral power in LF and HF bands may also be calculated; normalized tototal power between 0.04 and 0.4 Hz (TF=HF+LF) and expressed as % oftotal. Natural breathing rate of CHF patient, for example, can be ratherhigh, in the 0.3-0.4 Hz range.

The VLF band may be assumed to reflect periodic breathing frequency(typically 0.016 Hz) that can be present in CHF patients. It can beexcluded from the HF/LF power ratio calculations.

The powers of the LF and HF oscillations characterizing heart ratevariability (HRV) appear to reflect, in their reciprocal relationship,changes in the state of the sympathovagal (sympathetic toparasympathetic) balance occurring during numerous physiological andpathophysiological conditions. Thus, increase of HF contribution inparticular can be considered a positive response to carotid bodyblocking.

Another alternative method of assessing carotid body activity comprisesnuclear medicine scanning, for example with ocretide, somatostatinanalogues, or other substances produced or bound by the carotid body.

Furthermore, artificially increasing blood flow may reduce carotid bodyactivation. Conversely artificially reducing blood flow may stimulatecarotid body activation. This may be achieved with drugs know in the artto alter blood flow.

There is a considerable amount of scientific evidence to demonstratethat hypertrophy of a carotid body often accompanies disease. Ahypertrophied (i.e. enlarged) carotid body may further contribute to thedisease. Thus identification of patients with enlarged carotid bodiesmay be instrumental in determining candidates for therapy. Imaging of acarotid body may be accomplished by angiography performed withradiographic, computer tomography, or magnetic resonance imaging.

It should be understood that the available measurements are not limitedto those described above. It may be possible to use any single or acombination of measurements that reflect any clinical or physiologicalparameter effected or changed by either increases or decreases incarotid body function to evaluate the baseline state, or change instate, of a patient's chemosensitivity.

There is a considerable amount of scientific evidence to demonstratethat hypertrophy of a carotid body often accompanies disease. Ahypertrophied or enlarged carotid body may further contribute to thedisease. Thus identification of patients with enlarged carotid bodiesmay be instrumental in determining candidates for therapy.

Further, it is possible that although patients do not meet a preselectedclinical or physiological definition of high peripheral chemosensitivity(e.g., greater than or equal to about two standard deviations abovenormal), administration of a substance that suppresses peripheralchemosensitivity may be an alternative method of identifying a patientwho is a candidate for the proposed therapy. These patients may have adifferent physiology or co-morbid disease state that, in concert with ahigher than normal peripheral chemosensitivity (e.g., greater than orequal to normal and less than or equal to about 2 standard deviationsabove normal), may still allow the patient to benefit from carotid bodyablation. The proposed therapy may be at least in part based on anobjective that carotid body ablation will result in a clinicallysignificant or clinically beneficial change in the patient'sphysiological or clinical course. It is reasonable to believe that ifthe desired clinical or physiological changes occur even in the absenceof meeting the predefined screening criteria, then therapy could beperformed.

It is to be understood that the disclosure is not to be limited to thedisclosed embodiment(s). The disclosure also covers variousmodifications and equivalent arrangements included within the spirit andscope of the disclosure.

Exemplary Methods of Therapy:

Patients having CHF or hypertension concurrent with heightenedperipheral chemoreflex activity and sensitivity often react as if theirsystem was hypercapnic even if it is not. The reaction is tohyperventilate, a maladaptive attempt to rid the system of CO₂, thusovercompensating and creating a hypocapnic and alkalotic system. Someresearchers attribute this hypersensitivity/hyperactivity of the carotidbody to the direct effect of catecholamines, hormones circulating inexcessive quantities in the blood stream of CHF patients. The proceduremay be particularly useful to treat such patients who are hypocapnic andpossibly alkalotic resulting from high tonic output from carotid bodies.Such patients are particularly predisposed to periodic breathing andcentral apnea hypopnea type events that cause arousal, disrupt sleep,cause intermittent hypoxia and are by themselves detrimental anddifficult to treat.

It is appreciated that periodic breathing of Cheyne Stokes patternoccurs in patients during sleep, exercise and even at rest as acombination of central hypersensitivity to CO₂, peripheralchemosensitivity to O₂ and CO₂ and prolonged circulatory delay. Allthese parameters are often present in CHF patients that are at high riskof death. Thus, patients with hypocapnea, CHF, high chemosensitivity andprolonged circulatory delay, and specifically ones that exhibit periodicbreathing at rest or during exercise or induced by hypoxia are likelybeneficiaries of the proposed therapy.

Hyperventilation is defined as breathing in excess of a person'smetabolic need at a given time and level of activity. Hyperventilationis more specifically defined as minute ventilation in excess of thatneeded to remove CO₂ from blood in order to maintain blood CO₂ in thenormal range (e.g., around 40 mmHg partial pressure). For example,patients with arterial blood PCO₂ in the range of 32-37 mmHg can beconsidered hypocapnic and in hyperventilation.

For the purpose of this disclosure hyperventilation is equivalent toabnormally low levels of carbon dioxide in the blood (e.g., hypocapnia,hypocapnea, or hypocarbia) caused by overbreathing. Hyperventilation isthe opposite of hypoventilation (e.g., underventilation) that oftenoccurs in patients with lung disease and results in high levels ofcarbon dioxide in the blood (e.g., hypercapnia or hypercarbia).

A low partial pressure of carbon dioxide in the blood causes alkalosis,because CO₂ is acidic in solution and reduced CO₂ makes blood pH morebasic, leading to lowered plasma calcium ions and nerve and muscleexcitability. This condition is undesirable in cardiac patients since itcan increase probability of cardiac arrhythmias.

Alkalemia may be defined as abnormal alkalinity, or increased pH of theblood. Respiratory alkalosis is a state due to excess loss of carbondioxide from the body, usually as a result of hyperventilation.Compensated alkalosis is a form in which compensatory mechanisms havereturned the pH toward normal. For example, compensation can be achievedby increased excretion of bicarbonate by the kidneys.

Compensated alkalosis at rest can become uncompensated during exerciseor as a result of other changes of metabolic balance. Thus the inventedmethod is applicable to treatment of both uncompensated and compensatedrespiratory alkalosis.

Tachypnea means rapid breathing. For the purpose of this disclosure abreathing rate of about 6 to 16 breaths per minute at rest is considerednormal but there is a known benefit to lower rate of breathing incardiac patients. Reduction of tachypnea can be expected to reducerespiratory dead space, increase breathing efficiency, and increaseparasympathetic tone.

Therapy Example: Role of Chemoreflex and Central Sympathetic NerveActivity in CHF

Chronic elevation in sympathetic nerve activity (SNA) is associated withthe development and progression of certain types of hypertension andcontributes to the progression of congestive heart failure (CHF). It isalso known that sympathetic excitatory cardiac, somatic, andcentral/peripheral chemoreceptor reflexes are abnormally enhanced in CHFand hypertension (Ponikowski, 2011 and Giannoni, 2008 and 2009).

Arterial chemoreceptors serve an important regulatory role in thecontrol of alveolar ventilation. They also exert a powerful influence oncardiovascular function.

Delivery of Oxygen (O₂) and removal of Carbon Dioxide (CO₂) in the humanbody is regulated by two control systems, behavioral control andmetabolic control. The metabolic ventilatory control system drives ourbreathing at rest and ensures optimal cellular homeostasis with respectto pH, partial pressure of carbon dioxide (PCO₂), and partial pressureof oxygen (PO₂). Metabolic control uses two sets of chemoreceptors thatprovide a fine-tuning function: the central chemoreceptors located inthe ventral medulla of the brain and the peripheral chemoreceptors suchas the aortic chemoreceptors and the carotid body chemoreceptors. Asshown in FIG. 4, the carotid body 101, a small, ovoid-shaped (oftendescribed as a grain of rice), and highly vascularized organ is situatedin or near the carotid bifurcation 200, where the common carotid artery102 branches in to an internal carotid artery (IC) 201 and externalcarotid artery (EC) 206. The central chemoreceptors are sensitive tohypercapnia (high PCO₂), and the peripheral chemoreceptors are sensitiveto hypercapnia and hypoxia (low blood PO₂). Under normal conditionsactivation of the sensors by their respective stimuli results in quickventilatory responses aimed at the restoration of cellular homeostasis.

As early as 1868, Pflüger recognized that hypoxia stimulatedventilation, which spurred a search for the location of oxygen-sensitivereceptors both within the brain and at various sites in the peripheralcirculation. When Corneille Heymans and his colleagues observed thatventilation increased when the oxygen content of the blood flowingthrough the bifurcation of the common carotid artery was reduced(winning him the Nobel Prize in 1938), the search for the oxygenchemosensor responsible for the ventilatory response to hypoxia waslargely considered accomplished.

The persistence of stimulatory effects of hypoxia in the absence (aftersurgical removal) of the carotid chemoreceptors (e.g., the carotidbodies) led other investigators, among them Julius Comroe, to ascribehypoxic chemosensitivity to other sites, including both peripheral sites(e.g., aortic bodies) and central brain sites (e.g., hypothalamus, ponsand rostral ventrolateral medulla). The aortic chemoreceptor, located inthe aortic body, may also be an important chemoreceptor in humans withsignificant influence on vascular tone and cardiac function.

The carotid body exhibits great sensitivity to hypoxia (low thresholdand high gain). In chronic Congestive Heart Failure (CHF), thesympathetic nervous system activation that is directed to attenuatesystemic hypoperfusion at the initial phases of CHF may ultimatelyexacerbate the progression of cardiac dysfunction that subsequentlyincreases the extra-cardiac abnormalities, a positive feedback cycle ofprogressive deterioration, a vicious cycle with ominous consequences. Itwas thought that much of the increase in the sympathetic nerve activity(SNA) in CHF was based on an increase of sympathetic flow at a level ofthe CNS and on the depression of arterial baroreflex function. In thepast several years, it has been demonstrated that an increase in theactivity and sensitivity of peripheral chemoreceptors (heightenedchemoreflex function) also plays an important role in the enhanced SNAthat occurs in CHF.

Role of Altered Chemoreflex in CHF:

As often happens in chronic disease states, chemoreflexes that arededicated under normal conditions to maintaining homeostasis andcorrecting hypoxia contribute to increase the sympathetic tone inpatients with CHF, even under normoxic conditions. The understanding ofhow abnormally enhanced sensitivity of the peripheral chemosensors,particularly the carotid body, contributes to the tonic elevation in SNAin patients with CHF has come from several studies in animals. Accordingto one theory, the local angiotensin receptor system plays a fundamentalrole in the enhanced carotid body chemoreceptor sensitivity in CHF. Inaddition, evidence in both CHF patients and animal models of CHF hasclearly established that the carotid body chemoreflex is oftenhypersensitive in CHF patients and contributes to the tonic elevation insympathetic function. This derangement derives from altered function atthe level of both the afferent and central pathways of the reflex arc.The mechanisms responsible for elevated afferent activity from thecarotid body in CHF are not yet fully understood.

Regardless of the exact mechanism behind the carotid bodyhypersensitivity, the chronic sympathetic activation driven from thecarotid body and other autonomic pathways leads to further deteriorationof cardiac function in a positive feedback cycle. As CHF ensues, theincreasing severity of cardiac dysfunction leads to progressiveescalation of these alterations in carotid body chemoreflex function tofurther elevate sympathetic activity and cardiac deterioration. Thetrigger or causative factors that occur in the development of CHF thatsets this cascade of events in motion and the time course over whichthey occur remain obscure. Ultimately, however, causative factors aretied to the cardiac pump failure and reduced cardiac output. Accordingto one theory, within the carotid body, a progressive and chronicreduction in blood flow may be the key to initiating the maladaptivechanges that occur in carotid body chemoreflex function in CHF.

There is sufficient evidence that there is increased peripheral andcentral chemoreflex sensitivity in heart failure, which is likely to becorrelated with the severity of the disease. There is also some evidencethat the central chemoreflex is modulated by the peripheral chemoreflex.According to current theories, the carotid body is the predominantcontributor to the peripheral chemoreflex in humans; the aortic bodyhaving a minor contribution.

Although the mechanisms responsible for altered central chemoreflexsensitivity remain obscure, the enhanced peripheral chemoreflexsensitivity can be linked to a depression of nitric oxide production inthe carotid body affecting afferent sensitivity, and an elevation ofcentral angiotensin II affecting central integration of chemoreceptorinput. The enhanced chemoreflex may be responsible, in part, for theenhanced ventilatory response to exercise, dyspnea, Cheyne-Stokesbreathing, and sympathetic activation observed in chronic heart failurepatients. The enhanced chemoreflex may be also responsible forhyperventilation and tachypnea (e.g., fast breathing) at rest andexercise, periodic breathing during exercise, rest and sleep,hypocapnia, vasoconstriction, reduced peripheral organ perfusion andhypertension.

Dyspnea:

Shortness of breath, or dyspnea, is a feeling of difficult or laboredbreathing that is out of proportion to the patient's level of physicalactivity. It is a symptom of a variety of different diseases ordisorders and may be either acute or chronic. Dyspnea is the most commoncomplaint of patients with cardiopulmonary diseases.

Dyspnea is believed to result from complex interactions between neuralsignaling, the mechanics of breathing, and the related response of thecentral nervous system. A specific area has been identified in themid-brain that may influence the perception of breathing difficulties.

The experience of dyspnea depends on its severity and underlying causes.The feeling itself results from a combination of impulses relayed to thebrain from nerve endings in the lungs, rib cage, chest muscles, ordiaphragm, combined with the perception and interpretation of thesensation by the patient. In some cases, the patient's sensation ofbreathlessness is intensified by anxiety about its cause. Patientsdescribe dyspnea variously as unpleasant shortness of breath, a feelingof increased effort or tiredness in moving the chest muscles, a panickyfeeling of being smothered, or a sense of tightness or cramping in thechest wall.

The four generally accepted categories of dyspnea are based on itscauses: cardiac, pulmonary, mixed cardiac or pulmonary, and non-cardiacor non-pulmonary. The most common heart and lung diseases that producedyspnea are asthma, pneumonia, COPD, and myocardial ischemia or heartattack (myocardial infarction). Foreign body inhalation, toxic damage tothe airway, pulmonary embolism, congestive heart failure (CHF), anxietywith hyperventilation (panic disorder), anemia, and physicaldeconditioning because of sedentary lifestyle or obesity can producedyspnea. In most cases, dyspnea occurs with exacerbation of theunderlying disease. Dyspnea also can result from weakness or injury tothe chest wall or chest muscles, decreased lung elasticity, obstructionof the airway, increased oxygen demand, or poor pumping action of theheart that results in increased pressure and fluid in the lungs, such asin CHF.

Acute dyspnea with sudden onset is a frequent cause of emergency roomvisits. Most cases of acute dyspnea involve pulmonary (lung andbreathing) disorders, cardiovascular disease, or chest trauma. Suddenonset of dyspnea (acute dyspnea) is most typically associated withnarrowing of the airways or airflow obstruction (bronchospasm), blockageof one of the arteries of the lung (pulmonary embolism), acute heartfailure or myocardial infarction, pneumonia, or panic disorder.

Chronic dyspnea is different. Long-standing dyspnea (chronic dyspnea) ismost often a manifestation of chronic or progressive diseases of thelung or heart, such as COPD, which includes chronic bronchitis andemphysema. The treatment of chronic dyspnea depends on the underlyingdisorder. Asthma can often be managed with a combination of medicationsto reduce airway spasms and removal of allergens from the patient'senvironment. COPD requires medication, lifestyle changes, and long-termphysical rehabilitation. Anxiety disorders are usually treated with acombination of medication and psychotherapy.

Although the exact mechanism of dyspnea in different disease states isdebated, there is no doubt that the CBC plays some role in mostmanifestations of this symptom. Dyspnea seems to occur most commonlywhen afferent input from peripheral receptors is enhanced or whencortical perception of respiratory work is excessive.

Surgical Removal of the Glomus and Resection of Carotid Body Nerves:

A surgical treatment for asthma, removal of the carotid body or glomus(glomectomy), was described by Japanese surgeon Komei Nakayama in 1940s.According to Nakayama in his study of 4,000 patients with asthma,approximately 80% were cured or improved six months after surgery and58% allegedly maintained good results after five years. Komei Nakayamaperformed most of his surgeries while at the Chiba University duringWorld War II. Later in the 1950's, a U.S. surgeon, Dr. Overholt,performed the Nakayama operation on 160 U.S. patients. He felt itnecessary to remove both carotid bodies in only three cases. He reportedthat some patients feel relief the instant when the carotid body isremoved, or even earlier, when it is inactivated by an injection ofprocaine (Novocain).

Overholt, in his paper Glomectomy for Asthma published in Chest in 1961,described surgical glomectomy the following way: “A two-inch incision isplaced in a crease line in the neck, one-third of the distance betweenthe angle of the mandible and clavicle. The platysma muscle is dividedand the sternocleidomastoid retracted laterally. The dissection iscarried down to the carotid sheath exposing the bifurcation. Thesuperior thyroid artery is ligated and divided near its take-off inorder to facilitate rotation of the carotid bulb and expose the medialaspect of the bifurcation. The carotid body is about the size of a grainof rice and is hidden within the adventitia of the vessel and is of thesame color. The perivascular adventitia is removed from one centimeterabove to one centimeter below the bifurcation. This severs connectionsof the nerve plexus which surrounds the carotid body. The dissection ofthe adventitia is necessary in order to locate and identify the body. Itis usually located exactly at the point of bifurcation on its medialaspect. Rarely, it may be found either in the center of the crotch or onthe lateral wall. The small artery entering the carotid body is clamped,divided, and ligated. The upper stalk of tissue above the carotid bodyis then clamped, divided, and ligated.”

In January, 1965, the New England Journal of Medicine published a reportof 15 cases in which there had been unilateral removal of the cervicalglomus (carotid body) for the treatment of bronchial asthma, with noobjective beneficial effect. This effectively stopped the practice ofglomectomy to treat asthma in the U.S.

Winter developed a technique for separating nerves that contribute tothe carotid sinus nerves into two bundles, carotid sinus (baroreflex)and carotid body (chemoreflex), and selectively cutting out the latter.The Winter technique is based on his discovery that carotid sinus(baroreflex) nerves are predominantly on the lateral side of the carotidbifurcation and carotid body (chemoreflex) nerves are predominantly onthe medial side.

Neuromodulation of the Carotid Body Chemoreflex:

Hlavaka in U.S. Patent Application Publication 2010/0070004 filed Aug.7, 2009, describes implanting an electrical stimulator to applyelectrical signals, which block or inhibit chemoreceptor signals in apatient suffering dyspnea. Hlavaka teaches that “some patients maybenefit from the ability to reactivate or modulate chemoreceptorfunctioning.” Hlavaka focuses on neuromodulation of the chemoreflex byselectively blocking conduction of nerves that connect the carotid bodyto the CNS. Hlavaka describes a traditional approach of neuromodulationwith an implantable electric pulse generator that does not modify oralter tissue of the carotid body or chemoreceptors.

The central chemoreceptors are located in the brain and are difficult toaccess. The peripheral chemoreflex is modulated primarily by carotidbodies that are more accessible. Previous clinical practice had verylimited clinical success with the surgical removal of carotid bodies totreat asthma in 1940s and 1960s.

Additional Exemplary Embodiments

Any of the embodiments herein can include a forceps structure thatincludes means for pressing the ablation element against a wall of acarotid artery at a specific location adjacent the carotid septum.

Any of the embodiments herein can include first and second arms that areconfigured so that a force of contact distends the ablation elementabout 1 mm to 3 mm into a wall of a carotid artery.

Any of the embodiments herein can include a forceps structure thatincludes means for pressing the ablation element against a wall of acarotid artery.

Any of the embodiments herein can include an ablation element that ispositioned on the arm such that it engages a wall of the internal orexternal carotid artery delimiting a carotid septum.

Any of the embodiments herein can include an ablation element thatcomprises a surface adapted to contact a vessel wall adjacent thecarotid septum.

Any of the embodiments herein can include an ablation element that is anelectrode disposed on the first or the second arm.

Any of the embodiments herein can include first and second arms that areadapted to compress the carotid septum.

Any of the embodiments herein can include an arm actuator adapted tomove the first and second arms towards each other.

Any of the embodiments herein can include first and second arms that arefurther adapted to move away from each other toward a preset position.

Any of the embodiments herein can include an ablation element thatcomprises a first electrode disposed on the first arm and a secondelectrode disposed on the second arm.

Any of the embodiments herein can include first and second arms that areadapted to move from an undeployed configuration to a deployedconfiguration in which the first and second arms are further apart thanin the undeployed configuration.

Any of the embodiments herein can include a sheath adapted to containfirst and second arms during endovascular advancement.

Any of the embodiments herein can include a functional sheath diameterbetween 3 French and 12 French.

Any of the embodiments herein can include first and second arms that areadapted to move toward the deployed configuration as they emerge from asheath.

Any of the embodiments herein can include a sheath that is adapted to beadvanced toward first and second arms to move the first and second armstoward each other.

Any of the embodiments herein can include an ablation element that isconfigured to heat the target tissue to a temperature above 37° C. orabove 45° C.

Any of the embodiments herein can include one or more temperaturesensors positioned at the first and/or second arms.

Any of the embodiments herein can include a catheter that is configuredto be positioned against the carotid bifurcation saddle to position theablation element at a predetermined distance distal of the carotidbifurcation saddle.

Any of the embodiments herein can include a catheter that is configuredto place the ablation element against the wall of a carotid artery at aposition no more than 15 mm distal to the carotid bifurcation saddle.

Any of the embodiments herein can include an ablation catheter and anablation source operably connected to the ablation element of theablation catheter, and a user control comprising an ablation actuatoroperative to deliver an ablation agent from the ablation source to theablation element to ablate the target tissue.

Any of the embodiments herein can include an ablation source thatcomprises an RF generator.

Any of the embodiments herein can include an ablation element comprisesa first electrode disposed on the first arm and a second electrodedisposed on the second arm, and wherein the first and second electrodesare connected to opposite poles of an RF generator.

Any of the embodiments herein can include an ablation element thatcomprises a first electrode disposed on the first arm and a secondelectrode disposed on the second arm, and wherein the first and secondelectrodes are connected to the same poles of the RF generator.

Any of the embodiments herein can include a user control that isconfigured to specify or calculate treatment parameters to control adesired ablation.

Any of the embodiments herein can include first and second arms that areadapted to position the ablation element into contact with the vesselwall at a bifurcation between the external carotid artery and theinternal carotid artery.

Any of the embodiments herein can include an ablation element thatcomprises a sharp distal point adapted to penetrate through the vesselwall into the carotid septum.

Any of the embodiments herein can include contacting an ablation elementwith a vessel wall no more than 15 mm distal to a carotid bifurcationsaddle.

Any of the embodiments herein can include inserting an ablation elementinto the carotid septum.

Any of the embodiments herein can include grasping the carotid septumwith first and second arms.

Any of the embodiments herein can include compressing the carotid septumwith first and second arms.

Any of the embodiments herein can include moving the first and secondarms away from each other.

Any of the embodiments herein can include permitting the first andsecond arms to return toward a preset position.

Any of the embodiments herein can include moving first and second armstoward each other.

Any of the embodiments herein can include operating an arm actuator.

Any of the embodiments herein can include actuating an ablation elementto ablate the target tissue while first and second arms are engaged withthe artery walls.

Any of the embodiments herein can include using first and secondelectrodes to ablate the target tissue with RF energy.

Any of the embodiments herein can include heating the target tissue to atemperature above 37° C.

Any of the embodiments herein can include heating the target tissue to atemperature above 45° C.

Any of the embodiments herein can include delivering ablation energyfrom the ablation element to the target tissue for 30-120 seconds.

What is claimed is:
 1. A method of ablating at least one of a carotid body and afferent carotid body nerves, comprising: positioning an elongate medical device proximate a carotid artery bifurcation, the elongate medical device including an ablation element; positioning a distal protection member in an internal carotid artery, the distal protection member extending from an internal lumen within the elongate medical device, the distal protection member having a distal end region carrying a distal protection element; wherein positioning the distal protection member in the internal carotid artery comprises positioning a shaft in the internal carotid artery, wherein the shaft extends from the internal lumen within the elongate medical device, and wherein the distal protection element comprises a balloon carried by the shaft, wherein the balloon does not carry an energy delivery element thereon; deploying the distal protection element to a deployed configuration in the internal carotid artery to prevent emboli from traveling downstream of the deployed distal protection element; delivering ablation energy towards at least one of the carotid body and afferent carotid body nerves using the ablation element, the ablation element having been positioned in a carotid artery; and ablating the carotid body or afferent carotid body nerves with the ablation energy to treat at least one of hypertension, heart failure, and sleep apnea.
 2. The method of claim 1, wherein delivering ablation energy comprises delivering ablation energy towards at least one of the carotid body and afferent carotid body nerves using the ablation element that has been positioned in the internal carotid artery.
 3. The method of claim 1, wherein the delivering step comprises delivering ablation energy towards at least one of the carotid body and afferent carotid body nerves using the ablation element, which is carried by the elongate medical device.
 4. The method of claim 1, wherein the ablation element is an electrode.
 5. The method of claim 1, further comprising deflecting the elongate medical device into contact with the internal carotid artery. 